Circular RNAs (circRNAs) are endogenous RNA formed by the back splicing process. They are ubiquitous, stable, evolutionally conserved, and are tissue-specific. CircRNAs have numerous latent modes of action, from acting as sponges for microRNAs and RNA binding proteins to serving as transcriptional regulators, epigenetic alterations, etc. Dysregulated functioning of several circular RNAs leads to the progression of a plethora of diseases. CircRNAs have paved the way for advanced clinical studies as a novel method of disease diagnosis. This review systematically summarized and evaluated the role of differentially expressed circRNAs in four human diseases, including neurodegenerative diseases, diabetes, osteoarthritis, and cardiovascular diseases.