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Traditional preparation of African indigenous vegetables (AIVs) such as African black nightshade (Solanum nigrum) and African spiderplant (Cleome gynandra) involves either boiling and discarding the first water or lengthy boiling. Fermentation is considered a better alternative processing technique due to the enhanced retention of phytochemical contents and sensory properties. However, little is known about the impact of lactic acid fermentation on the phytochemical content, antioxidant capacity, sensory acceptability and microbial safety of the African black nightshade and African spiderplant. This study aimed to ferment AIVs using combined starter cultures (Lactobacillus fermentum and Lactococcus lactis) and further determine their effect on the phytochemical content (phenolic compounds and flavonoids), antioxidant capacity, sensory acceptability and microbial safety of the vegetables. There was a marked increase in phenol and flavonoid contents in all fermented vegetables (p < 0.05). The highest phenol content was 228.8 mg/g GAE (gallic acid equivalent) in the starter-culture-inoculated African black nightshade, while flavonoid content was 10.6 mg/g QE (quercetin equivalent) in the same. Starter-culture-inoculated AIVs presented significantly higher antioxidant capacity with a 60–80% radical scavenging activity compared to levels in uninoculated batches (p < 0.05). Fermented vegetables were more liked than the boiled vegetables and were microbiologically safe. In conclusion, lactic fermentation of AIVs increased phytochemical contents (phenolic compounds and flavonoids), maintained antioxidant capacity and improved product safety and sensory acceptability. Therefore, fermentation and consumption of the African indigenous vegetables are to be encouraged. Full article