A practical and novel approach has been developed for the synthesis of oleanolic acid based chromene analogues. Different α,β-unsaturated carbonyl and chromene derivatives of oleanolic acid were synthesized and evaluated for their anticancer activity. Compounds 6e, 6k, 7e and 7g showed significant anticancer activity within the IC₅₀ range of 12.23–39.04 μg mL⁻¹. The promising derivatives 7e and 7g were further analyzed for their effects on the cell cycle and apoptosis in A-549 and MDA-MB-231 cells, and it was depicted that 7e and 7g triggered apoptosis in A-549 and MDA-MB-231 cells and arrested the cell population in the G₂/M phase. The anticancer activity of the most active analogue 7g occurred through microtubule destabilization (IC₅₀: ∼3.6 μg mL⁻¹), and it was found to be non-toxic against human erythrocytes. The compounds 7e and 7g significantly inhibited the proinflammatory cytokines TNF-α and IL-6.