The coronavirus disease 2019 (COVID-19) pandemic has affected the mental health of individuals worldwide, and the risk of psychiatric sequelae and consequent mental disorders has increased among the general population, health care workers and patients with COVID-19. Achieving effective and widespread prevention of pandemic-related psychiatric sequelae to protect the mental health of the global population is a serious challenge. Salidroside, as a natural agent, has substantial pharmacological activity and health effects, exerts obvious neuroprotective effects, and may be effective in preventing and treating psychiatric sequelae and mental disorders resulting from stress stemming from the COVID-19 pandemic. Herein, we systematically summarise, analyse and discuss the therapeutic effects of salidroside in the prevention and treatment of psychiatric sequelae as well as its roles in preventing the progression of mental disorders, and fully clarify the potential of salidroside as a widely applicable agent for preventing mental disorders caused by stress; the mechanisms underlying the potential protective effects of salidroside are involved in the regulation of the oxidative stress, neuroinflammation, neural regeneration and cell apoptosis in the brain, the network homeostasis of neurotransmission, HPA axis and cholinergic system, and the improvement of synaptic plasticity. Notably, this review innovatively proposes that salidroside is a potential agent for treating stress-induced health issues during the COVID-19 pandemic and provides scientific evidence and a theoretical basis for the use of natural products to combat the current mental health crisis.