This study aimed to investigate the influences of fermentation at 37 °C for 3 days by different lactic acid bacterium strains, Lactobacillus plantarum (17a), Weissella cibaria (21), Leuconostoc pseudomesenteroides (56), W. cibaria (64) or L. plantarum (75), on color, pH, total soluble solids (TSS), phenolic compounds and antioxidant activity of African nightshade (leaves). Results indicated fermentation with L. plantarum 75 strain significantly decreased the pH and total soluble solids, and increased the concentration of ascorbic acid after 3 days. L. plantarum 75 strain limited the color modification in fermented nightshade leaves and increased the total polyphenol content and the antioxidant activity compared to the raw nightshade leaves. Overall, L. plantarum75 enhanced the functional potential of nightshade leaves and improved the bioavailability of gallic, vanillic acid, coumaric, ferulic ellagic acids, flavonoids (catechin, quercetin and luteolin) and ascorbic acid compared to the other lactic acid bacterium strains. Correlation analysis indicated that vanillic acid and p-coumaric acid were responsible for the increased antioxidant activity. Proximate analysis of the fermented nightshade leaves showed reduced carbohydrate content and low calculated energy.