To study the toxicological profile and anti-hyperlipidemic effects of Spondias mombin leaves methanolic extract in experimental rats. Preventing high levels of lipids or its recurrence is currently one of the key aims of clinical and experimental studies. This study was carried out to investigate the toxicological profile and anti-hyperlipidemic effects of methanolic extract of leaves of Spondias mombin. The acute toxicity study was carried out where the limited dose of 2000 mg/kg body weight was administered to five rats at 48 h intervals. The interpretation was prepared and recorded for 24 h. In the sub-acute toxicity study, rats were treated with 250, 500, and 1000 mg/kg doses of the extract every 24 h for 28 days. The hematological, biochemical, and histopathological tests of treated animals were carried out at the end of the test. The anti-hyperlipidemic activity of plant extract (100, 200 mg/kg) was studied on Triton-X-100 induced hyperlipidemia in rats. Histopathological changes in the liver of rats were examined. For acute and subacute treatment, the extract did not reveal any signs of toxicity or mortality, or any significant effects on hematological, biochemical parameters, and histopathology of organs. The extract demonstrated an important anti-hyperlipidemic result by decreasing the serum levels of cholesterol, TGs, LDL, VLDL, and enhancing HDL. Taking up the evidence of the experimental study, we can conclude that the methanolic extract of Spondias mombin leaves helps in declining hyperlipidemia in rats and it can be safely used for a period of 28 days to treat hyperlipidemia.