The adverse effect of CsA on the morphology and function of kidney makes nephrotoxicity its key limiting factor. However, the mechanisms of chronic CsA-provoked nephrotoxicity seem to be multifactorial. An in vitro study carried out with LLC-PK1 cell line has provided evidence that the major side effect of CsA might exhibit significant alterations on intracellular calcium pathway. Further, cytochrome C and caspase-3 expressions were also augmented during Cyclosporine A (CsA) exposure, which eventually led to apoptosis. Yet, the underlying molecular mechanism behind the effect of CsA on calcium signaling pathway is inadequate. The present study unravels the status of calcium signaling, cytochrome C and caspase-3 in CsA-induced apoptotic mechanism and the role of sulphated polysaccharides will be evaluated for its beneficial role in the above mechanism. Cotreatment of CsA-induced LLC-PK1 cells with sulphated polysaccharides (extracted from marine brown algae, “Sargassum wightii” prevented abnormal increase in intracellular calcium concentration due to CsA administration, as reflected by an intense fluorescence using Fura-2AM staining. Decrease in caspase activation and cytochrome C level on sulphated polysaccharides administration also shows the anti-apoptotic role of sulphated polysaccharides through its antioxidant nature.