The majority of research on nanomaterials has been concentrated on metal nanoparticles since they are easily made and manipulated. Nanomaterials have shown a wide range of applications in biology. Nevertheless, their bioactivity declines due to their extreme susceptibility to chemical and physical stimuli. The goal of encapsulating these nanomaterials in a matrix is gradually being pursued, which boosts their affordability, stability, and usability. Metal-organic frameworks, often known as MOFs, have the potential to be the best platforms for encapsulating metal nanoparticles due to their well-defined frameworks, persistent porosity, and flexibility in modification. In this investigation, we report the synthesis and optimization of polyvinylpyrrolidone (PVP)-stabilized Se (0) nanoparticles and novel Se@ZIF-8 by chemical method. The sizes and morphologies of Se (0) and Se@ZIF-8 were affected by the ratios of Se/Zn2+ and [hmim]/Zn2+ used. The optimized Se@ZIF-8 nanoparticles exhibited a particle size and zeta potential of 319 nm and -34 mv respectively. Transmission electron microscopy displayed spherical morphology for Se(0) nanoparticles, whereas the surface morphology of novel Se@ZIF-8 nanoparticles was drastically changed to hexagonal shaped structures with smooth surface morphologies in scanning electron microscopy. The DTA, TG/DTG, XRD analysis confirmed the presence of novel Se incorporated ZIF-8 nanoparticulate framework. The synthesized novel Se@ZIF-8 nanoparticles showed efficient antibacterial activity as evidenced by low MIC values. Interestingly, these Se@ZIF-8 NPs not only inhibited biofilm formation in S. marcescens, but also effectively eradicated mature biofilms by degrading the eDNA of the EPS layer. It was observed that Se@ZIF-8 targeted the Quroum Sensing pathway and reduced its associated virulence factors production. This work opens up a different approach of Se@ZIF-8 nanoparticles as novel antibiotics to treat biofilm-associated infections caused by S. marcescens and offer a solution for antimicrobial resistance.