The development of antibacterial coatings for footwear components is of great interest both from an industry and consumer point of view. In this work, the leather material was developed taking advantage of the intrinsic antibacterial activity and coloring ability of selenium nanoparticles (SeNPs). The SeNPs were synthesized and implemented into the leather surface by using ultrasonic techniques to obtain simultaneous coloring and functionalization. The formation of SeNPs in the solutions was evaluated using UV/Vis spectroscopy and the morphology of the NPs was determined by transmission electron microscopy (TEM). The treated leather material (leather/SeNPs) was characterized by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The effects of SeNPs on the coloration and antibacterial properties of the leather material were evaluated. The results revealed that the NPs were mostly spherical in shape, regularly distributed, and closely anchored to the leather surface. The particle size distribution of SeNPs at concentrations of 25 mM and 50 mM was in the range of 36–77 nm and 41–149 nm, respectively. It was observed that leather/SeNPs exhibited a higher depth of shade compared to untreated ones, as well as excellent fastness properties. The results showed that leather/SeNPs can significantly enhance the antibacterial activity against model of bacteria, including Gram-positive bacteria (Bacillus cereus) and Gram-negative bacteria (Pseudomonas aeruginosa, Salmonella typhi and Escherichia coli). Moreover, the resulting leather exhibited low cytotoxicity against HFB4 cell lines. This achievement should be quite appealing to the footwear industry as a way to prevent the spread of bacterial infection promoted by humidity, poor breathability and temperature which promote the expansion of the microflora of the skin.