Cellulose nanocrystals (CNC)‐based foams are promising tissue engineering materials that may facilitate implant‐tissue integration and allow localized and controlled drug delivery. Herein, hybrid CNC‐based foams, which are ultralightweight (30–100 mg cm−3), highly porous (>95%), ominiphilic and superabsorbent (1500–3000 wt% of water and/or toluene uptake) are obtained by the in situ condensation of poly(ethylene glycol) ditriethoxysilyl (TES‐PEG‐TES) into a 3D network, where silsesquioxane nanoparticles (SS‐NP) are the crosslinking nodes, and CNC are entrapped forming ionic interactions, in a supramolecular structure. In a new approach, using 3‐mercaptopropyltrimethoxysilane, sulfhydryl groups are inserted on the SS‐NP periphery and S‐nitrosated to enable the functionalization of SS‐NP with S‐nitrosothiol groups, which can nitric oxide (NO), in a process triggered by the hydration of the foams and modulated by their supramolecular structure. CNC‐SS‐PEG foams exhibit elevated thermal and structural stability, compressive strength compatible with various soft human tissues, and NO release rates (1–18 pmol mg−1 min−1) within the range of the beneficial NO actions. Thus, the CNC‐SS‐PEG foams herein described represent a new platform of supramolecular hybrid materials for localized delivery of NO, with potential uses in tissue engineering and other biomedical applications. Supramolecular cellulose nanocrystal‐based foams are produced by the in situ condensation of poly(ethylene glycol)ditriethoxysilyl, generating a 3D hybrid network. Sulfhydryl groups at the periphery of silsesquioxane nanoparticles are S‐nitrosated to release nitric oxide spontaneously upon hydration with rates controlled by the supramolecular structure. Foams show potential application as platforms for localized nitric oxide delivery.