Most biosensors relying on antibodies as recognition elements fail in harsh environment conditions such as elevated temperatures, organic solvents or proteases because of antibody denaturation, and require strict storage conditions with defined shelf-life, thus limiting their applications in point-of-care and resource-limited settings. Here, a metal-organic framework (MOF) encapsulation is utilized to preserve the biofunctionality of antibodies conjugated to nanotransducers. This study investigates several parameters of MOF coating (including growth time, surface morphology, thickness and precursor concentrations) that determine the preservation efficacy against different protein denaturing conditions in both dry and wet environments. A plasmonic biosensor based on gold nanorods as the nanotransducers is employed as a model biodiagnostic platform. The preservation efficacy attained through MOF encapsulation is compared to two other commonly employed materials (sucrose and silk fibroin). The results show that MOF coating outperforms sucrose and silk fibroin coatings under several harsh conditions including high temperature (80 °C), dimethylformamide and protease solution, owing to complete encapsulation, stability in wet environment and ease of removal at point-of-use by the MOF. We believe this study will broaden the applicability of this universal approach for preserving different types of on-chip biodiagnostic reagents and biosensors/bioassays, thus extending the benefits of advanced diagnostic technologies in resource-limited settings.