A series of arylidene analogues of Meldrum's acid were synthesized and evaluated for in vitro antimalarial and antioxidant activities for the first time. The influence of various physico-chemical parameters such as dielectric constant (epsilon), donor number (DN), acceptor number (AN), hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), and solubilizing power of the solvents on Meldrum's acid anion generation and thus on promoting the Knoevenagel condensation of Meldrum's acid with aryl aldehydes has been discussed. Five compounds 9l, 9m, 9n, 9r, and 9s were found to be most active against Plasmodiumfalciparum with IC(50) values in the range of 9.68-16.11 microM. Compound 9l exhibited the most potent antimalarial activity (IC(50) 9.68 microM). The compounds were also found to possess antioxidant activity when tested against DPPH and ABTS free radicals.