Isoniazid (INH) and rifampicin (RIF) are the two main drugs used for the management of tuberculosis. They are often used as a fixed drug combination, but their delivery is challenged by suboptimal solubility and physical instability. This study explores the potential of active pharmaceutical ingredient-ionic liquids (API-ILs) to improve the physicochemical and pharmaceutical properties of INH and RIF. Antitubercular drugs, INH, or RIF, were paired with different counter ions (ascorbic acid (AsA), citric acid (CA), tartaric acid (TA), benzoic acid (BA), salicylic acid (SA), and p-amino salicylic acid (PAS)) using the solvent evaporation method. INH and RIF API-ILs were formed successfully using AsA and CA counter ions. IL formation was examined and analyzed using Fourier transform infrared (FTIR) spectroscopy, x-ray powder diffraction (XRPD), and polarized optical microscopy (POM). XRPD and POM confirmed their amorphous nature, while FTIR analysis demonstrated the contribution of hydrogen bonding to IL formation. IL formation enhanced the storage stability of the INH + RIF mixture in the presence of CA. Moreover, RIF-CA IL significantly increased the rate and extent of RIF dissolution. An effect that is unattainable with the RIF/CA physical mixture. Thus, API-IL formation not only enhances RIF dissolution but also facilitates the preparation of stable, compatible INH-RIF combinations.