Recently, chitosan/regenerated silk fibroin (CS/SF) films have been developed for daily disposable contact lenses. This study further explored the versatility of using CS/SF films in contact-lens-based ophthalmic delivery for multiple charged drugs. The selected model drugs, the negatively charged 5(6)-carboxyfluorescein (CF), the zwitterion rhodamine B (RB), and the noncharged acetaminophen (APAP), were individually loaded into the CS/RSF films by soaking. The non-charged APAP could not be loaded into the CS/SF films, whereas the charged CF and RB were successfully loaded. The drug loading capacity increased with soaking time and reached its equilibrium at 3 h. Furthermore, the drug loading capacity and release characteristics could be controlled by adjusting the CS/SF ratio in the film, which is useful for tailoring various treatments. The loading capacity and release duration of the negatively charged CF increased with CS content, while those of the zwitterion RB increased with SF content. In addition, a prolonged drug release exceeding 12 h could be obtained for both drugs. In summary, the CS/SF films are promising biomaterials for contact-lens-based ophthalmic delivery of various charged drugs, which is beneficial for reducing the drug side effects and administration frequency.