A new fusidic acid-loaded hydrogel film was prepared via the solvent casting technique using alginate and Aloe vera. The hydrogel films were optimized using different ratios of sodium alginate, Aloe vera, and glycerin. The films containing 10% glycerin (w/w of alginate) exhibited the best appearance. Incorporating Aloe vera influenced the thickness, swelling behavior, water vapor permeability, and drug release profile of the hydrogel films. Higher Aloe vera content resulted in thicker films (up to a certain ratio), increased swelling, reduced water vapor permeability, and a prolonged drug release of up to 93% over 12 h. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of key functional groups and the interaction between the hydrogel components. The study suggests that the combination of sodium alginate, Aloe vera, and glycerin can improve the mechanical properties and drug release profiles of hydrogel films, making them a promising option for enhanced topical drug delivery and wound healing applications.