Background: Indirubin is the main bioactive component of the traditional Chinese medicine Indigo naturalis and is a bisindole alkaloid. Multiple studies have shown that indirubin exhibits good anticancer, anti-inflammatory and neuroprotective properties. Methods: The purpose of this review is to provide a summary of the pharmacological mechanisms of indirubin and its derivatives. Results: Indirubin and its derivatives exert anticancer effects by regulating the expression of cyclin-dependent kinases (CDKs), GSK-3β, Bax, Bcl-2, C-MYC, matrix metalloproteinases (MMPs), and focal adhesion kinase (FAK) through the PI3K/AKT/mTOR, nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK), JAK/signal transducer and activator of transcription 3 (STAT3) pathways and other signaling pathways. We also reviewed the anti-inflammatory and neuroprotective properties of indirubin and its derivatives. Conclusion: The findings of recent studies assessing indirubin and its derivatives suggest that these compounds can be used as potential drugs to treat tumors, inflammation, neuropathy and bacterial infection. © 2022 The Authors