Antioxidants are bioactive molecules that safeguard cells against oxidative stress, a condition that induces cellular injury and is implicated in the development of various chronic diseases. Diabetes mellitus is a long-term metabolic disorder marked by persistent hyperglycemia resulting from inadequate insulin secretion, impaired insulin action, or both. This study aimed to investigate the in vitro antioxidant and antidiabetic potentials of the methanolic leaf extract of C. pentandra using an experimental model of Drosophila melanogaster subjected to a high-sucrose diet. The antioxidant potential of the extract was evaluated using several assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power (FRAP), lipid peroxidation inhibition, reducing power capacity, and reduced glutathione (GSH) quantification. The antidiabetic activity of the plant was assessed through in vitro α-amylase inhibition and in vivo analysis using D. melanogaster exposed to a high-sucrose diet. A total of thirty-five (35) D. melanogaster were utilized, divided into five experimental groups. Metformin (16 mg) was employed as the reference drug, while C. pentandra extract was administered at concentrations of 2 and 4 mg. The experiment was conducted over a ten-day period, after which the flies were analyzed for glucose and total protein levels. The in vitro antioxidant evaluation of C. pentandra methanolic extract demonstrated substantial activity across all assays, with notably higher lipid peroxidation inhibition (84.73%) and reducing power (20.52%) compared to the standard antioxidant, butylated hydroxytoluene (BHT) (50.13% and 17.26%, respectively) at 500 µg/mL. The extract exhibited a concentration-dependent increase in α-amylase inhibitory activity (21.83%, 22.55%, and 23.60%), although the values remained lower than those of the standard drug, acarbose (52.76%, 54.20%, and 68.04%) at 500, 750, and 1000 µg/mL, respectively. These findings suggest that the extract’s ability to modulate glucose metabolism may improve with increasing concentrations. In in vivo assays, metformin produced the lowest glucose concentration (40 mg/dL), while the 4 mg C. pentandra extract-treated group showed reduced glucose levels (60 mg/dL) compared to the 2 mg group (150 mg/dL). Protein concentration analysis revealed no significant differences (P < 0.05) among the extract-treated groups, whereas both the normal (non-diabetic) and metformin-treated controls exhibited similar protein levels (80 mg/dL). Overall, C. pentandra methanolic extract demonstrated potent lipid peroxidation inhibition and superior reducing power, indicating its potential to mitigate oxidative stress. Furthermore, its glucose-lowering effect suggests a promising antidiabetic activity, possibly through enhanced insulin sensitivity.