Two simple, rapid, accurate, and precise spectrophotometric methods were developed for the determination of silver sulfadiazine (SSD) and sodium hyaluronate (SH) in the presence of methyl and propyl paraben. The methods were applied after the division of each zero-order spectrum of SSD and SH by the spectrum of paraben to exclude it. Method A, a dual wavelength of ratio spectra method, is based on selection of two wavelengths at which the peak amplitude of SH is the same but different for SSD, so wavelengths of 258.0 and 312.6 nm were used to determine SSD in the presence of SH. Other two wavelengths were selected at 208.0 and 238.4 nm for the determination of SH in the presence of SSD. Method B was first derivative spectrophotometry for the determination of SSD and fourth derivative spectrophotometry for the determination of SH. Peak amplitudes were measured at 236.0 and 225.2 nm for SSD and SH, respectively. The proposed methods were validated according to ICH recommendations. The calibration curves for the proposed methods were linear over a concentration range of 1.0–10 and 25–250 µg/mL for SSD and SH, respectively. The specificity of the proposed methods was tested using different laboratory prepared mixtures of both drugs showing high specificity of SSD and SH with accepted recovery values. The proposed methods have been successfully applied for the determination of SSD and SH in pharmaceutical dosage forms without interference from additives. [ABSTRACT FROM AUTHOR]