<p>The present study aimed to perform phytochemical investigation of various fractions of the aerial parts of <i>Senecio laetus</i> Edgew for its bio-constitution and to pharmacologically evaluate these fractions for antioxidant and antiproliferative activities against breast cancer (MCF-7) and colon carcinoma (HCT-116) cell lines. Phytochemical screening and characterization of compounds was carried out as per standard procedures. Extracts were subjected to GC-MS analysis for identification and characterization of constituents. The antioxidant activity was carried out using DPPH, ferric ion reducing power assay, and nitric oxide radical inhibition assays. In vitro antiproliferative activity of the extracts was carried out using MCF-7 (breast cancer) and HCT-116 (colon carcinoma) cancer cell lines by MTT assay, colony formation assay, and wound healing assay. Phytochemical screening showed the presence of alkaloids, flavonoids, carbohydrates, glycosides (cardiac and anthraquinone), tannins, triterpenoids, phenolic compounds, and phytosterols. GC-MS analysis showed the presence of 54 compounds. Ethyl acetate and methanolic extract exhibited the maximum amount of phenolic content compared to dichloromethane and hexane fractions. Antioxidant capacities were shown highest in ethyl acetate and methanolic fractions. The antiproliferative activity was found to be concentration dependent, with dichloromethane fraction more effective than ethyl acetate and hexane fractions against both the MCF-7 and HCT-116 cancer cell lines. The results indicate that <i>S. laetus</i> Edgew has a promising antioxidant and antiproliferative potential as shown by its activity against MCF-7 (breast carcinoma) and HCT-116 (colon carcinoma) cancer cell lines.</p>