Mallotus oppositifolius, a plant species in the genus Mallotus, is traditionally employed to treat various health conditions, including diabetes, malaria, and inflammation. In this study, we investigated the subchronic toxicological profile of the methanolic extract of Mallotus oppositifolius stem (MEMOS). The subchronic toxicity of MEMOS was assessed in Wistar albino rats (both males and females). The treated animals were administered doses of 500 mg/kg and 1000 mg/kg of body weight orally for 28 days, while the control group received distilled water. During the treatment period, there were no reported deaths among the study rats. Male rats administered 1000 mg/kg of MEMOS exhibited a significant increase in body weight. Remarkably, MEMOS had no discernible impact on the weight of organs or blood components. The biochemical markers associated with oxidative stress such as glutathione and malondialdehyde remained unperturbed. Metabolic parameters like glycemia, creatinine, ALAT, ASAT, and total proteins mirrored those of the control group. Treated rats exhibited lower cholesterol levels compared to their control counterparts. MEMOS demonstrated safety in terms of fatalities and organ function, yet it also hinted at intriguing effects on body weight and cholesterol levels.