Arginine has been a mainstay in biological formulation development for decades. To date, the way arginine modulates protein stability has been widely studied and debated. Here, we employed a hydrophobic polymer to decouple hydrophobic effects from other interactions relevant to protein folding. While existing hypotheses for the effects of arginine can generally be categorized as either direct or indirect, our results indicate that direct and indirect mechanisms of arginine co-exist and oppose each other. At low concentrations, arginine was observed to stabilize hydrophobic polymer folding via a sidechain-dominated direct mechanism, while at high concentrations, arginine stabilized polymer folding via a backbone-dominated indirect mechanism. Upon introducing partially charged polymer sites, arginine destabilized polymer folding. Further, we found arginine-induced destabilization of a model virus similar to direct-mechanism destabilization of the charged polymer and concentration-dependent stabilization of a model protein similar to the indirect mechanism of hydrophobic polymer stabilization. These findings highlight the modular nature of the widely used additive arginine, with relevance in the information-driven design of stable biological formulations.