The nutritive value of mushroom melon cake was investigated. Our study indicates that the raw melon possessed high moisture, protein and fat content of 87.15±0.03, 45.20±0.01, and 48.83±0.01 g/100 dry weight, respectively. However, it was low in fibre and carbohydrate. Another major component of the melon cake, Pleurotus tuber regium proximate composition gave 48.20±0.02, 15.50±0.02, 0.84±0.02, 3.31±0.02 and 1.63±0.03 for moisture, protein, fat, fibre and carbohydrate, respectively. Following 96 hours of fermentation, the protein content increased from 46.47±0.02 to 47.78±0.01 in the group aided by Baker’s yeast and was higher than the natural fermentation group whose protein went from 45.55±0.05 to 47.50±0.02. Phytochemical screening showed the presence of cardiac glycosides in Combretum micranthum but not in Pleurotus tuber regium. C. miranthum also showed good antimicrobial activity against the isolated microorganisms from the contaminated the melon. Further work should be carried out on C. micranthum antimicrobial properties.