Depression is a psychiatric disorder that has a significant health burden on patients and their families. Unfortunately, the current antidepressant medications that mainly target monoamine neurotransmitters have limited efficacy. Recent evidence has indicated that neuroinflammation participates in the genesis and development of depression, and interacts with other factors involved in depression. Therefore, exploring effective anti-inflammatory medications could be beneficial for the development of new treatment options for depression. Sirtuins are a unique class of nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylases, which have seven members that can affect multiple downstream targets by deacetylation activity. Among these seven members, SIRT1 and SIRT2 have been shown to participate in the pathophysiology of inflammation in numerous studies. Thus, in this short article, we review the association of SIRT1 and SIRT2 activity and depression, and evidence of the effects of SIRT1 and SIRT2 modulators on inflammation in vitro and depressive-like behaviours in vivo.