Introduction: Diabetes mellitus, once described as the epidemic of the 21st century affects over 415 million people globally. The beneficial effects of most conventional anti-diabetics wanes-off with time aside their various side effects. Newer and effective anti-diabetics with little or no side effect are therefore necessary. Scanty works exist on the effect of L-citrulline especially in the setting of type-2 diabetes mellitus (T2DM). Aim: This study aimed to determine the effect of L-citrulline in high-fat diet (HFD)- and dexamethasone-induced T2DM in male Wistar rats. Methods: Thirty male Wistar rats, 8-12 weeks old, weighing 200-250 grams were randomly assigned into six groups of five rats each. Group I received normal diet throughout the experiment, while T2DM was induced in groups II-VI with HFD for 21 days and dexamethasone intraperitoneally (1 mg/kg) for 7 days. After the induction, group III received metformin 100 mg/kg/day orally, while groups IV-VI received L-citrulline 200 mg/kg/day, 400 mg/kg/day and 800 mg/kg/day respectively for 21 days. Fasting blood glucose (FBG) level, lipid profile and some biomarkers of oxidative stress were determined. Results were expressed as mean±S.E.M and values at P<0.05 were considered statistically significant. Ethical approval was obtained from the Ahmadu Bello University Committee on Animal Use and Care (Approval No.: ABUCAUC/2020/71). Results: The FBG levels were significantly reduced by L-citrulline in a dose-dependent manner (192.5±3.4 mg/dL, 181.8±1.2 mg/dL and 174.8±2.8 mg/dL at 200, 400 and 800 mg/kg/day respectively). L-Citrulline markedly lowered the total cholesterol levels at 200 mg/kg (55.2±0.64 mg/dL), 400 mg/kg (57.8±1.19 mg/dL) and 800 mg/kg (63.1±1.50 mg/dL) compared to the diabetic control (149.8±2.68 mg/dL). There were similar decreases observed in the LDL and triglyceride levels. Significant elevations in the HDL levels were also seen at all doses of L-citrulline compared to diabetic control (24.6±1.1 mg/dL). Compared to the diabetic group (42.0±0.42 µmol/L), L-citrulline markedly decreased the MDA concentrations (20.7±0.81 µmol/L, 22.2±0.75 µmol/L and 22.1±0.39 µmol/L at 200, 400 and 800 mg/kg/day respectively). The depletions of SOD observed in the diabetic group (13.0±0.44 µmol/mg), was ameliorated by L-citrulline at all does especially at 800 mg/kg/day (23.7±0.78 µmol/mg; P<0.001). Similar increase was also recorded in the CAT activity at 800 mg/kg/day (14.6±0.54 ng/dL; P<0.001) compared to the diabetic group (10.8±0.41 ng/dL). The GSH level was augmented by L-citrulline at all doses, especially at 400 mg/kg/day (46.4 ± 0.53 µmol/mg protein; P<0.001), compared to the diabetic group (22.9±0.69 µmol/mg protein). Conclusion: L-Citrulline possesses a hypoglycemic, anti-dyslipidemic and antioxidant effects in HFD- and dexamethasone-induced T2DM in male Wistar rats. Key words: Antioxidant, L-citrulline, anti-dyslipidemic, type-2 diabetes mellitus.