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<i>Coronopus didymus</i> (Brassicaceae) commonly known as lesser swine cress has been reported to be used for its pharmacological activities. This study aimed to evaluate the medicinal potential of <i>C. didymus</i> extracts against cancer, diabetes, infectious bacteria and oxidative stress and the identification of bioactive compounds present in these extracts. The effects of using different solvents for the extraction of <i>C. didymus</i> on the contents of major polyphenols and biological activities were investigated. Plant sample was shade dried, ground to a fine powder, and then soaked in pure acetone, ethanol and methanol. The highest contents of major polyphenols were found in methanol-based extract, i.e., chlorogenic acid, HB acid, kaempferol, ferulic acid, quercetin and benzoic acid with 305.02, 12.42, 11.5, 23.33, 975.7 and 428 mg/g of dry weight, respectively, followed by ethanol- and acetone-based extracts. The methanol-based extract also resulted in the highest antioxidant activities (56.76%), whereas the highest antiproliferative (76.36) and alpha glucosidase inhabitation (96.65) were demonstrated in ethanol-based extracts. No antibacterial property of <i>C. didymus</i> was observed against all the tested strains of bacteria. Further studies should be focused on the identification of specific bioactive compounds responsible for pharmacological activities.