Nature's creations with spiky topological features typically exhibit intriguing surface adhesive properties. From micrometer-sized pollen grains that can easily stick to hairy insects for pollination to nanoscale virus particles that are highly infectious toward host cells, multivalent interactions are formed taking advantage of rough surfaces. Herein, this nature-inspired concept is employed to develop novel drug delivery nanocarriers for antimicrobial applications. A facile new approach is developed to fabricate silica nanopollens (mesoporous silica nanospheres with rough surfaces), which show enhanced adhesion toward bacteria surfaces compared to their counterparts with smooth surfaces. Lysozyme, a natural antimicrobial enzyme, is loaded into silica nanopollens and shows sustained release behavior, potent antimicrobial activity, and long-term total bacterial inhibition up to 3 days toward Escherichia coli. The potent antibacterial activity of lysozyme-loaded silica nanopollens is further demonstrated ex vivo by using a small-intestine infection model. Our strategy provides a novel pathway in the rational design of nanocarriers for efficient drug delivery.