Cardiac fibrosis is a pathogenic factor of many cardiovascular diseases (CVD), which seriously affects people's life, and health and causes huge economic losses. Increasing evidence has shown that peroxisome proliferator-activated receptors (PPARs) can regulate the progression of cardiac fibrosis. For the first time, this review systematically summarizes the literature on cardiac fibrosis from the perspective of PPARs from 2010 to 2020. Moreover, the role of each PPARs in cardiac fibrosis was clarified in this scientific revision from the perspectives of pharmacologically active substances, known agonists, natural extract compounds, and nucleic-acid-based drugs in different CVD models. Furthermore, the combination of multiple PPARs on the treatment of cardiac fibrosis is discussed. This scientific review provides new ideas for targeting PPARs in the treatment of cardiac fibrosis and provides strategies for the development of new, safe, and effective pharmacological antagonists against cardiac fibrosis based on PPAR activity.