Depression is one of the most common but serious psychiatric disorders affecting millions of people globally, which has become increasingly prevalent during the past few decades. To alleviate this challenging health and social burden, various therapeutic strategies have been developed to achieve efficient treatments for depression. In particular, plenty of chemical ingredients of natural origin have been investigated as new direct antidepressants or served as adjuvants to improve the current treatment outcomes of existing antidepressant drugs. Among them, curcumin, a natural compound derived from the herbCurcuma longa, exhibits a wide range of pharmacological properties and has been considered a potent antidepressant drug with diverse mechanisms including monoaminergic imbalances (associated with serotonin, dopamine, noradrenaline and glutamate), effect on neurotransmitters, neuroprogression, the hypothalamic-pituitary-adrenal (HPA) axis disturbances, dysregulated inflammation and immune pathways, oxidative and nitrosative stress, and mitochondrial disturbances. In this review, multiple potential mechanisms of curcumin for treating depression demonstrated in either animal or human studies are summarized. To better understand the significant role of curcumin, specific emphasis will be placed on the aetiopathogenesis of depression. Finally, current pre-clinical/clinical trials and ongoing challenges of curcumin used for antidepressant treatments will be discussed and their future outlooks will be briefly presented.