African indigenous vegetables (AIVs) because of their nutrient density have the unique potential to reduce micronutrient deficiencies in sub-Saharan Africa, yet some may also contain anti-nutritive compounds. Vegetable nightshades from Solanum americanum, Solanum nigrum, Solanum scabrum and Solanum villosum are among the major AIVs used as a leafy vegetables and consumed regularly in many countries in sub-Sahara Africa. These under-recognized food crops have not been subjected to extensive studies for their nutritional and antinutritive factors. In this study, 15 entries of the vegetable nightshades were field-grown and the leaves which are the consumed product of commerce chemically profiled by LC/ESI-MS. Twenty-three flavones, eight saponins, and two glycoalkaloids along with a phenolic acid of chlorogenic acid were identified by MS and UV data. Anti-nutrient glycoalkaloids were quantified as total aglycones after acidic hydrolysis using MS detection and found to be within safe-consumption thresholds by comparison with the glycoalkaloid level in the globally consumed Solanum member eggplants. Edible nightshades were also found to be sources of β-carotene, vitamin E and total polyphenols and exhibited high antioxidant activity. Results of this study support that consumption of vegetable nightshades are safe from the presence of glycoalkaloids and thus, can contribute to the reduction of micronutrient deficiency in sub-Sahara Africa.