Absorption and emission (at 77 K) spectra and amperometric cyclic voltammograms of dibucaine and primaquine were recorded at different concentrations and pH values. While dibucaine shows distinguishable photophysical properties for neutral, hydrogen-bonded, and protonated species, primaquine at 77 K aggregates to form an excited-state double-proton-transfer dimer (i.e., a J-type excimer) at concentrations higher than 5 x 10(-5) M and in the pH range 2.5-5.5. Dibucaine is electrochemically stable, but primaquine is not. The electrochemical instability of primaquine is probably associated with the observation that the 1 x 10(-4) M primaquine in acetonitrile displays a highly accentuated signal of cyclic voltammogram in the reduction reaction H+. The proton dissociative nature of primaquine supports the NMR measurement that the exchange of C-5 aromatic proton in primaquine at pH <4 is unusually fast. The acidic nature of primaquine resulted from the dissociation of C-5 aromatic proton could assist the uptake of the antimalarial drugs. The spectroscopic investigations of native bacteriorhodopsin (bR) and delipidated deionized bR incorporating with two drugs show that dibucaine interacts with the protein of bR, while primaquine affects its lipid and denatures the purple membrane. The results are discussed in light of the pharmacological actions of dibucaine (a local anesthetic drug) and of primaquine (an antimalarial drug).