Background: Mallotus oppostifollous is a shrub used folklorically in traditional medicine for the treatment and management of different diseases including infections, wounds, and inflammation across tribes where they are found including South East Nigeria. This study was aimed to toxicity, renal-protective and hepato-protective effect of crude methanol extract of M. oppositifolius honey mixture in rats. Methods: The powdered leaf extracts of M. oppositifolius was extracted by cold maceration using methanol. The acute toxicity, hepatotoxicity and renal-toxicity profile of the crude extract of M. oppositifolius were carried out using standard laboratory procedures. Results: The result showed that Mallotus oppostifollous administered orally had LD50 above 5000mg/kg and showed no toxic effect on the blood, kidney and liver of the rats when used orally. It stabilized the blood hematology and biochemical parameters. It showed no significant elevation on the creatinine, blood urea nitrogen and uric acid and therefore showed that the honey combination could have a stabilizing effect on the vital organs of the rats. Conclusion: We therefore conclude that the crude extract of Mallotus oppostifollous has no toxic effect against the kidney, liver and blood parameters and therefore is safe for consumption as a phytomedicine. Therefore, we recommend its continued usage for the treatment of diseases.