Abstract: This study investigated the effect of fermentation on the microbial, proximate and anti-nutrient contents of melon (Cucumis melo L.) husk using standard analytical techniques. The microorganisms isolated and identified were Staphylococcus aureus, Bacillus subtilis, B. megatarium, B. licheniformis, Leuconostoc mesenteriodes, Lactobacillus plantarum, Rhizopus stolonifer and Saccharomyces ludwigii. There was a significant increase in the bacterial count from 12x103-37x103 CFU g–1 and in the fungi population from 1.67x103-11.67x103 SFU g–1 as the fermentation progressed. The raw melon husk had no lactic acid bacteria before fermentation, but a total colony count of 32.3x103 CFU g–1 was observed after 24 h of fermentation. Proximate analysis revealed that fermentation process increased the protein and carbohydrate contents significantly (p<0.05) from 2.61-6.54 and 13.88-31.66%, respectively after 72 h of fermentation. Anti-nutrient assay revealed the presence of cyanogenic glycosides, phytic acid, tannins, phytates, oxalates and phenols. Anti-nutrient contents decreased significantly (p<0.05) as the fermentation process progressed. Phenol content slightly increased from 0.13-0.35% after 72 h of fermentation. The overall results obtained from this study revealed that fermentation process enhanced the protein and carbohydrate contents of melon husk and significantly (p<0.05) reduced the anti-nutrient contents. The level of its nutritive value indicated that it can be used as an agricultural feed for herbivores, which would solve a waste disposal problem and help in turning the waste around us for economic gains.