The aromatic amino acid tryptophan is the most susceptible protein residue involved in various photosensitized adverse effects. Of these processes, the tryptophan photosensitization induced by methylene blue has been well studied. A predominant type II photosensitizing activity, mediated by singlet oxygen, has been already demonstrated on various models. The purpose of this study is to compare this photosensitization system with that induced by naproxen, belonging to the class of non-steroidal anti-inflammatory drugs. For this compound, a type I (radical) and type II (singlet oxygen) cooperative mechanism of photoinduced damage was previously proposed. This study represents an example of testing drugs on the simple experimental model of amino acid residues in proteins. Particular emphasis is dedicated to modifications caused by the formation of drug photomediated toxic species, such as reactive oxygen species (ROS). This is achieved following the kinetics of photodegradation of the sensitizers and of the amino acid, as well as the formation of their photoproducts and by evaluation of quantum yields of the various processes. Tryptophan photoproducts represent biomarkers of oxidative damage indicative for protein photooxidation and for the molecular mechanism of photosensitization; some of these have been identified for the first time as UVA photosensitization products. The pattern of Trp photoproducts formed by the two compounds differs and is specific for each type of sensitization process. These observations support extending the investigation to systems of increasing molecular complexity, that is Trp in isolated proteins and in cells and represent an effort to provide a simplified rationale of the complex picture coming out from literature data and our experimental results.