Cisplatin is recognized as active anticancer drug for treatment of various human cancers; however, it exhibits numerous undesirable side effects as nephrotoxicity resulting in a significant treatment complication. Brown algae polysaccharides are widely used for pharmaceutical industries due to their antioxidant and anti-inflammatory properties. Chitosan nanoparticles (CSNPs) have demonstrated significant promise for use in the delivery of drugs. Nanoparticles were prepared using the ionic gelation technique using chitosan (CS) and sodium tripolyphosphate (STPP). All nanoparticles revealed spherical shape. The average particle sizes of the fabricated nanoparticles were between 270 ± 82 nm for CSNPs and 148 ± 35 nm for polysaccharides loaded on CSNPs (PS-CSNPs). The main purpose of this study was to detect the effect of brown alga (Turbinaria triquetra) polysaccharides loaded and unloaded on chitosan nanoparticles against Cisplatin-induced nephrotoxicity in rats.  Forty-two male Wistar rats were divided into 7 equal groups. Control untreated group, CSNPs group, polysaccharide (PS) group, PS loaded on chitosan nanoparticles (PS-CSNPs) group, cisplatin (Cis) group, Cis + PS group, and Cis + PS-CSNPs group. Serum urea and creatinine, creatinine clearance, renal malondialdehyde (MDA), nitric oxide (NO), and paraoxonase 1 (PON 1) were determined. Results: Brown alga PS either loaded or unloaded on CSNPs efficiently attenuated Cis-induced nephrotoxicity evidenced by significant reduction in serum urea and creatinine, renal MDA and NO along with significant elevation in creatinine clearance and renal PON 1 compared to the Cis-treated group. However, the improvement was higher in the nephrotoxic group treated with the loaded PS. Conclusion: The current study revealed that the nanoencapsulation of brown alga PS using CSNPs has marked ameliorative effects against Cis nephrotoxicity more better than PS do alone. The observed results offer a new therapeutic approach in attenuating Cis-induced nephrotoxicity.