Current therapies for toxoplasmosis rely on a few drugs, most of which have severe side effects, and seeking ideal therapies for different types of toxoplasmosis is a long-term and challenging mission. Research and development (R&D) of novel drugs against Toxoplasma gondii (T. gondii) has focused on two main directions, the structural modification of lead compounds and natural products. Here we summarize the recent advances in the development of anti-T. gondii drugs from these two perspectives and provide comprehensive insights, reflecting on the advantages and selected molecules in each field. This review also focuses on the current obstacles to the development of novel anti-T. gondii agents, proposes comprehensive solutions, and facilitates future development.