Nephrolithiasis is a multifactorial urological disorder strongly associated with oxidative stress and altered enzymatic redox balance. Serum oxidoreductases—including catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and xanthine oxidase (XO)—play central roles in regulating reactive oxygen species (ROS) and renal injury. Pharmacological interventions for nephrolithiasis commonly involve alpha-adrenergic receptor antagonists such as tamsulosin, and urinary alkalinizing agents such as potassium citrate. While tamsulosin facilitates ureteral stone expulsion by reducing smooth muscle tone, potassium citrate alters urinary pH and reduces calcium oxalate supersaturation. Recent studies suggest that the combined administration of tamsulosin and potassium citrate not only improves stone clearance rates but also modulates systemic oxidative stress responses. This review consolidates current evidence regarding serum oxidoreductase responses to tamsulosin–potassium citrate combination therapy in patients with nephrolithiasis, highlighting molecular mechanisms, clinical outcomes, and future research directions.