Using steady-state spectroscopic and zeta potential methods, we have unraveled the interaction of the purple membrane (PM) and bacteriorhodopsin (bR) with various surfactants below their critical micelle concentrations. We found that the charged hydrophilic heads of ionic surfactants play a role in perturbing the structure and conformation of PM and bR and that ionic surfactants of opposite charges cause opposing effects. Specifically, the addition of a low concentration (0.2 mM) of the cationic surfactant cetyl trimethylammonium bromide (CTAB) is capable of neutralizing the negatively charged lipids on the PM surface via electrostatic forces. This results in increased hydrophobicity of PM that leads to the aggregation of PM. In contrast, denaturation of PM and bR was observed when the anionic surfactant sodium dodecyl sulfate (SDS) was added to the PM suspensions. The attachment of SDS to the PM surface increases the solubility of PM and causes a loose crystalline structure. As the SDS concentration is increased to more than 3 mM, the secondary structure of the constituents of bR is significantly distorted, and the protonated Schiff base is hydrolyzed to form free retinal. The addition of the neutral surfactant diethylene glycol mono-n-hexyl ether (C6E2) does not significantly influence the PM and bR, meaning most of their original properties are preserved. We conclude that the addition of surfactants might cause the aggregation or solubilization of the membrane protein, depending on the signs of the charged hydrophilic heads of the surfactants and the charges of the membrane protein surface. Aggregation results when the surfactant and protein have opposite charges, whereas solubilization results when the surfactant and protein have the same charge.