We have investigated the anti-oxidative and glucose-lowering effects of 70% methanolic extract of H. heteroclita fruit pulp (MHE). Anti-oxidative property of MHE was assessed by free radical scavenging assays and compound level screening by LC-MS profiling. In silico analysis and in vivo preclinical validation were also performed using molecular docking and alloxan-induced diabetic model, respectively. MHE showed high anti-oxidant activity in DPPH radical scavenging assay with an IC50 of 0.37 μg/mL. The LC-MS profile of MHE substantiated the presence of p-hydroxy acids including benzoic, salicylic, p-coumaric, o-coumaric, caffeic, protocatechuic, gentisic, 2,4-dihydroxybenzoic, gallic, vanillic, syringic, and ferulic acids. Among these, caffeic acid was the most likely compound to interact with 1R0E at Val70, Ala83, Lys85, Gly97, Asp133, Val135, Leu188, Cys199, and Asp200, and with 1Q4L at Ile62, Ala83, Asp133, Tyr134, Val135, Arg141, and Val170. Treatment of rats with MHE showed significant reduction in serum glucose levels as compared to control rats. Taken together, the results show that MHE has compounds with anti-diabetic effect, which could be partially due to the anti-oxidant effects of the active components in MHE.