Sulfated polysaccharides are widely found in seaweed. These compounds have several commercial uses, especially in the industrial sector. However, the renal effects of these substances remain to be investigated. This work aimed to evaluate the renal effects of the total sulfated polysaccharides (TSP) obtained from the seaweed Gracilaria cornea on the renal system. The TSP significantly increased the perfusion pressure (PP) and the renal vascular resistance (RVR). TSP decreased the urinary flow at the lowest concentration tested but increased at higher concentrations. The TSP caused a significant decrease in the glomerular filtration rate (GFR) and transport of sodium, potassium and chloride. The compounds caused mild histological changes, which indicated tubular and glomerular damages. The TSP caused significantly decreased in the viability of MDCK cells, which presented apoptotic signs and late apoptotic cell death. In conclusion, TSP caused significant changes in renal physiology and morphology. However, further research is required to elucidate the signaling pathways involved in the apoptotic effects of TSP and evaluate the potential of these molecules on drug development.