Aim: To improve the solubility and antibacterial activity of trimethoprim (TMP) by preparing its multicomponent crystals with malic acid (MA). Methods: Multicomponent crystals of TMP-MA were prepared by solvent co-evaporation. The solid-state properties were characterised by powder X-ray diffraction (PXRD), differential thermal analysis (DTA), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM) analyses. The solubility was investigated in an aqueous medium, while the antibacterial activity against Escherichia coli was investigated using the agar disk diffusion method. Results: The PXRD pattern of the TMP-MA binary system differed from the starting materials, supporting the formation of a new crystalline phase (equimolar ratio). The DTA thermogram showed a single, sharp, endothermic peak at 212.5 °C attributable to the TMP-MA multicomponent crystal's melting point. FT-IR spectroscopy showed a solid-state interaction involving proton transfer between TMP and MA. The multicomponent crystal displayed a 2.5-fold higher solubility and had increased antibacterial activity compared to TMP alone. Conclusions: The TMP-MA binary system forms salt-type multicomponent crystals that significantly increase solubility and antibacterial activity. Multicomponent crystal formation is a viable technique for modifying the physicochemical properties of active pharmaceutical ingredients.