Nigella sativa's thymoquinone (TQM), a water-insoluble phytonutrient exhibits nephroprotective effects. This study intends to develop a self-micellizing solid dispersion (SMSD) of TQM for better biopharmaceutical and nephroprotective performance. Soluplus®-based SMSD of TQM was created and tested for physicochemical properties, solubility, and pharmacokinetics in rats. Plasma creatinine, blood urea nitrogen (BUN), nephrotoxic indicators, and oxidative stress biomarkers were also tested. During SMSD preparation, TQM was found amorphous, boosting solubility. Minimal band changes between TQM and Soluplus® indicate insignificant drug-carrier interactions. SMSD-TQM generated fine micelles in water, improving TQM's solubility by 97.8% in 60 min. SMSD-TQM was 4.9 times more bioavailable orally in rats than crystalline TQM. In a rat model of acute renal damage by cisplatin (6 mg/kg, i.p.), SMSD-TQM (10 mg-TQM/kg, p.o.) reduced blood creatinine and BUN by 56% and 63.2%, respectively. These findings imply that SMSD-TQM may be a potent dosage option for enhancing TQM's nutrient value.