Double‐hydrophilic, semi‐interpenetrating (semi‐IPN) hydrogels are synthesized by encapsulating hydrophilic polyvinylpyrrolidone (PVP) linear chains in structure‐defined 1,2‐bis‐(2‐iodoethoxy)ethane (BIEE)‐crosslinked (poly(2‐(dimethylamino)ethyl methacrylate) (pDMAEMA) hydrogels. A series of semi‐IPN double‐hydrophilic hydrogels are prepared in which the pDMAEMA/BIEE content is kept the same and only the PVP content is varied, from 0 up to 33 wt%. The mechanical properties of the water‐swollen hydrogels are experimentally evaluated under unconfined compressive loading conditions, while a nonlinear hyperelastic constitutive equation is used to predict their mechanical response. No significant difference is found in the mechanical response of the semi‐IPN PVP/pDMAEMA/BIEE hydrogel containing 5 wt% PVP compared to the pDMAEMA/BIEE analog, however, for greater loading percentages (15 and 33 wt% of PVP), the semi‐IPN hydrogels exhibit less stiffness/higher ductility. Furthermore, in vitro biocompatibility studies are carried out for the pDMAEMA/BIEE and the semi‐IPN PVP/pDMAEMA/BIEE, indicating that both the formulations exhibit no toxicity in cultured cells.