Phytochemicals are known for their therapeutic effects through diverse mechanisms such as therapeutic modulators, substrate ligands, receptor ligands, enzyme cofactors, enzymes precursors, toxins scavengers, microbial growth inhibitors, therapeutic agents, and therapeutic enhancers in the treatment of various diseases and ailments. Folklorically, the indigenous people of Nigeria have used Desmodium velutinum (Fabaceae) for treatment of disease conditions such as headache, fever, diarrhea toothaches, ulcers, anti-oxidants, and pains. This study investigated the toxicity, and anti-ulcer effects of a combination of methanol leaf extract of Desmodium velutinum and honey in rats. Anti-ulcer studies were carried out using absolute ethanol rat models of ulceration. The rats were distributed into ten groups of five rats each. Group 1 served as a negative control, group 2 served as a positive control, group 3 served as untreated control, the test groups: groups 4 to 6 received crude extract of Desmodium velutinum at doses of 100, 250, and 500 mg/kg respectively, groups 7 to 9 received a combination of 1 ml honey and crude leaf extract of Desmodium velutinum at doses of 100, 250 and 500 mg/kg while group 10 received 1 ml of honey only. The acute toxicity showed that the extract caused no death in the mice at 5000mg/kg and therefore the LD50 is above 5000mg/kg. The result also showed that 500 mg/kg of the crude extract and 1 ml honey had 42.9% and 71.76 % inhibition of ulceration respectively, while their combination had 100% inhibition of ulceration among the rats treated with the combinations. The combination of methanol leaves extract of Desmodium velutinum and honey exhibited gastrotherapeutic effect in rats and suggest its continued usage as an antiulcer agent for the treatment of ulcer.