Chia seeds (Salvia hispanica) are currently consumed by varied populations as superfoods due to their protective, functional and antioxidant properties. They are becoming one of the most popular plant-based foods that contain the greatest amount of nutrients particularly omega-3 fatty acid (α-linolenic acid), protein, fats and minerals. Therefore, Chia seeds are considered a functional food with pronounced health benefits and deemed useful in cardiovascular health. The objectives of this study were to determine the proximate composition, mineral contents, fatty acid profiles and phytochemical screening of chia seeds grown in East Africa (Kenya and Uganda); investigate the in vitro efficacy of chia seed extracts on the inhibition of α-amylase and pancreatic lipase activities; determine the effect of ground chia seeds/extracts on postprandial glycaemia, body weight, hematological parameters and cellular morphology in rats; and evaluate the dose effect of chia seed extracts on plasma glycaemia, body weight changes, lipemia, liver enzymes and hematological parameters in male Wistar rats fed with fructose and lard. Samples, black chia Among’ura-Teso (BCAT), black chia Kigumba (BCK), black chia Molo (BCM), Black chia Ongariama-Teso (BCOT) and White chia Bukembo (WCB) were collected from Kenya and Uganda. Official methods of analysis (AOAC International) were adopted for proximate analysis; minerals were determined by Atomic absorption spectrophotometer, and fatty acid profiles were analyzed by Gas chromatography. Phytochemicals and assays on pancreatic lipase and α-amylase enzymes were conducted using standard methods. Acarbose and Orlistat were used as positive controls. For animal studies, 44 male Wistar rats were divided into two experimental groups (acute experiment-20 rats and dose effect experiment-24 rats). In acute experiment, 20 male Wistar rats were assigned into three experimental groups and a control (n =5). Each experimental group received 10 g/20 g fructose/lard. Group 1 and 3 were supplemented with 20 g chia seed extract while group 2 received ground chia seeds only. Control group received rat pellets only. Rat pellets and water were given ad libitum in all groups. All diets were fed for a period of 28 days. In a dose effect experiment, 24 male Wistar rats were randomly assigned into three experimental groups (low dose, medium dose and high dose of 6 animals each) and a control. The control group received 6g/12g fructose/lard only, the experimental groups were also given 6g/12g of fructose/lard and in addition received 12g/kg, 18 g/kg and 24 g/kg body weight of chia seed extract for low dose, medium dose and high dose respectively. Rat pellets and water were given ad libitum to all groups. The diets were fed daily for a period of 8 weeks. Statistical analysis was conducted using STATA version 14.1, a one-way analysis of variance (ANOVA) used F-test to determine the variability between group means, significance was accepted at probability (p < 0.05). Results on proximate composition indicated high contents of protein, fat and fiber. The fatty acid profiles revealed great amounts of α-linolenic acid (ALA) (45.29-56.99 %) followed by linoleic acid (15.9-20.28%) and oleic acid (6.88-11.58%). Although the amount of ALA was high compared to other fatty acids analyzed in all samples, the difference was not significant (p = 0.7391). Mineral determination (mg/100g) displayed high contents of potassium (492.96-862.98), phosphorous (486.45-569.45), calcium (297.47- 429.09) and magnesium (192.22-202.97) while considerable amount was observed for iron, zinc, manganese, and copper. There was a significant difference (p = 0.0001) in mineral content between BCK and WCB with exception of phosphorus. For the in vitro studies, BCAT displayed the highest inhibition on α-amylase activity with the IC₅₀ value of 104.51 ± 1.22 μg/ml and 72.87 ± 1.95 μg/ml for ethanolic and methanolic extracts respectively, however they were significantly lower (p = 0.0001) than that of acarbose. On the other hand, BCAT exhibited the strong pancreatic lipase inhibitor with IC₅₀ value of 90.28 ± 5.84 μg/ml and 96.33 ± 12.22 μg/ml) for ethanolic and methanolic extracts respectively, followed by BCM and BCK. Orlistat indicated a significantly higher (p = 0.001) IC₅₀ (54.88 ± 2.27 μg/ml), establishing its relative potency as pancreatic lipase inhibitor than chia seed extracts. In acute experiment, there was a gradual increase in body weight of chia seeds/extract fed rats as compared to fructose/lard group. There was an increase in postprandial blood glucose levels in group 1 from week I to IV contrary to groups supplemented with chia seeds/extract. Complete blood counts showed a significant increase (p = 0.008) in mean corpuscular hemoglobin concentration, basophils (p = 0.035), platelets (p = 0.025) and red cell distribution width (p = 0.008) in experimental groups compared to control. In a dose effect experiment, platelets were significantly lower (p = 0.009) in low dose group compared to a control and high dose groups (p = 0.046). For liver enzymes, aspartate aminotransferase (AST) was significantly lower (p = 0.039) in low dose group as compared to medium and high dose groups (p = 0.028), while bilirubin was significantly lower (p = 0.038) in high dose as compared to control group. Serum lipids such as high density lipoprotein cholesterol (HDL-C) increased significantly (p = 0.041) in high dose group than the control while low density lipoprotein cholesterol (LDL-C) decreased significantly (p = 0.035) in high dose group as compared to control and medium dose groups (p = 0.021) The East African grown chia seeds, exhibited high amounts of α-linolenic acid, proteins, fats, fiber, and minerals. The seeds inhibited the pancreatic lipase and α-amylase activities, these enzymes are responsible for the digestion of fats and carbohydrates respectively. Inhibition of these enzymes may help decrease hyperglycemia and hyperlipidemia the risk factors for cardiovascular disease (CVD). The positive impact showed on LDL-C, HDL-C and triglycerides in rats fed on diet high in fat and fructose suggest the potential of chia seeds in inhibiting progression of atherosclerosis hence controlling type 2 diabetes mellitus, obesity and CVD. Generally, these results highlight that chia seeds could be among the preferred natural food sources for the primary prevention of cardiovascular diseases. Therefore, we suggest its moderate incorporation in diets as a healthy food ingredient.