Polysaccharide hydrogels constitute a structurally diverse class of biological macromolecules with a wide range of physicochemical properties. They also constitute important members of the family of industrial water-soluble polymers. They find application in Pharmacy as binders, disintegrants, suspending, emulsifying and sustaining agents. According to the International Pharmaceutical Excipients Council (IPEC), an excipient must have an established safety profile. Hence, in the present study, in vitro cytotoxicity on Vero and HEp-2 cell lines, and in vivo acute toxicity in rats were carried out to establish the safety of polysaccharide hydrogels from the seeds of Plantago ovata and Ocimum basilicum. The in vitro cytotoxicity was determined by MTT and SRB assays. In the in vivo acute toxicity, the effects of three different doses of hydrogels (100, 200 and 400 mg/kg body weight) on food and water intake, body weight, biochemical and hematological parameters were studied. The results of in vitro did not show any cytotoxicity on both the cell lines used. In the in vivo acute toxicity, the hydrogels did not show any toxic symptoms in all three dose levels. This establishes the safety of the selected hydrogels. Hence, they can be used as excipients in pharmaceutical dosage forms.