Antimycoplasma drugs paved the way for the treatment of mycoplasma infections even before the vaccines were developed. Macrolides, tetracyclines, or aminoglycosides were being used for long, incorporating quinolones in the newer regimes. Former drug classes target protein synthesis, whereas the latter one targets DNA synthesis. These drugs proved quite effective and helped minimize severity and loss to farmers. However, prolonged use of antibiotics may have serious concerns of drug resistance, side effects, and drug residues in food animal products. In addition, despite treating mycoplasma infection, some drugs create a carrier state of infection that can spread the infection without being recognized. Hence, novel alternate therapeutics need to be explored to overcome these limitations whilst checking the antibiotic resistance with regular antibiotic sensitivity tests, which need to be standardized for different mycoplasma. Future therapeutics are needed under the prevailing situations of emerging and transboundary spread of mycoplasma infections.