This study reports on the antioxidant, anti-diabetic and cytotoxic properties of different extracts of two Senecio species, Senecio vulgaris and Senecio inaequidens. Leaves of the latter are used as food in specific populations of Southern of Africa. Both investigated species of Senecio were found to possess different biological activities. S. inaequidens extracts possess a greater antioxidant activity in comparison with S. vulgaris. Highly significant and dose-dependent performance was obtained with the methanolic and dichloromethane extracts of S. vulgaris and the n-hexane extract of S. inaequidens regarding cytotoxic activity on cancer cell lines, while none of the extracts demonstrated activity on normal cell line MRC-5. Both Senecio species also show appreciable alpha-amylase inhibition, particularly the methanolic and dichloromethane extracts, and this may confer anti-diabetic properties on the extract.