Methods and compositions are provided which inhibit the apoptotic activity associated with oxidative stress in many disease states. According to the invention, inhibition of chemical cleavage of PKC.delta. by caspase-3 results in reduction of apoptosis. Novel peptide inhibitors with the amino acid motif Asp Ile Pro Asp (SEQ ID NO:5) are also disclosed. The peptides are useful as inhibitors of PKC.delta.-mediated apoptosis and oxidative stress, and other diseases regulated by a catalytically active PKC.delta..