Lignocellulosic materials have garnered significant attention in recent years to generate biomaterials, but nothing has been investigated with cacao residues of significant importance in Ecuador. This study's objective was to generate porous, three-dimensional sponges from cacao pod shell mesocarp with potential use in biomaterial application. Discs from the mesocarp of cacao pod shells were subjected to neutral, acid, and alkaline treatments, at 25oC and 100oC, followed by washing and lyophilization. Sponge composition was evaluated, with the alkaline treatment resulting in the highest cellulose content and the lowest percentage of lignin, with the removal of hemicellulose corroborated by FITR. The sponges presented high water absorption capacities, which increased with the treatment temperature; mainly, the alkaline generated structures had the largest capacity. The sponges' porosity also depended on the treatment, with the acid and alkaline treatments generating larger pores, which significantly grew with treatment temperature. Preliminary in vitro cytotoxicity tests were carried out using Wharton's jelly mesenchymal stem cells, according to ISO 10993.5.2009, with none of the materials being cytotoxic; however, those with greater lignin contents resulted in lower cell viability. In general, it is considered that the alkaline generated sponges presented the more significant potential for biomaterial applications, which could be further tested with In vitro cell proliferation and differentiation studies and possible in vivo assays.