A novel, green, sensitive, and cost-effective kinetic-derivative spectrophotometric method has been developed and validated for the quantitative determination of loxoprofen sodium (LXP) in pharmaceutical dosage forms. The method is based on the kinetic monitoring of the oxidative coupling reaction of LXP under optimized conditions, employing the fixed-time approach for calibration. First-derivative spectrophotometry was applied to enhance selectivity and eliminate spectral interferences from formulation excipients. The reaction was carried out in an aqueous medium, eliminating the need for toxic organic solvents and fulfilling the principles of green analytical chemistry. Beer's law was obeyed over the concentration range of 0.5–20 µg/mL. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.15 and 0.46 µg/mL, respectively. The method was fully validated in accordance with ICH Q2(R1) guidelines. The results were statistically comparable to those obtained using the reference HPLC method. The proposed method was successfully applied to the determination of LXP in commercially available tablet formulations with satisfactory recoveries of 98.5–101.4%.