The effect of an acid component and carbon chirality in the ligand framework on the bioactivity of the resulting Pd(II) pincer complexes was elucidated by evaluating their cytotoxicity against different solid and blood cancer cell lines, apoptosis induction ability, and P-glycoprotein (P-gp) affinity, which revealed the high anticancer potential of some of them, and in particular, the potential to overcome drug resistance associated with P-gp overexpression. Here, PGP is linked to hematopoietic and lymphoid system neoplasm.