Molybdenum disulfide (MoS2) holds great promise for antibacterial applications owing to its strong photothermal performance and biocompatibility. Most of its antibacterial explorations have sought enhanced antibacterial potency through designing new hybrid inorganic materials, the relationship between its physiochemical properties and antibacterial activities has yet to be explored. This work is the first to investigate the combination effects of different sized and functionalized MoS2 sheets on their antibacterial activities. The bacterial capture abilities of 3 µm mannosylated, galactosylated, and glucosylated sheets, as well as 300 nm mannosylated sheets, all with similar sugar densities, are compared. Only mannosylated MoS2 sheets are found to agglutinate normal Escherichia coli (E. coli) and large mannosylated MoS2 sheets show the strongest E. coli agglutination. Despite slightly weaker photothermal performance under near-infrared (NIR) laser irradiation, large mannosylated MoS2 sheets exhibit higher antibacterial activity than the smaller sheets. By much stronger specific multivalent binding, large sheets capture E. coli more efficiently and compensate for their reduced photothermal activity. Besides providing a facile approach to eliminate E. coli bacteria, these findings offer valuable guidance for future development of 2D nanomaterial-based antibacterial agents and filter holder materials, where large-functionalized sheets can capture and eliminate bacteria powerfully.