Depression is one of the most common behavioral and psychological symptoms in people with Alzheimer's disease (AD). To date, however, the molecular mechanisms underlying the clinical association between depression and AD remained elusive. Here, we study the relationship between memory impairment and depressive-like behavior in AD animal model, and investigate the potential mechanisms. Male SD rats were administered amyloid-β oligomers (AβOs) by intracerebroventricular injection, and then the depressive-like behavior, neuroinflammation, oxidative stress, and the serotonergic system were measured in the brain. Sulforaphane (SF), a compound with dual capacities of anti-inflammation and anti-oxidative stress, was injected intraperitoneally to evaluate the therapeutic effect. The results showed that AβOs induced both memory impairment and depressive-like behavior in rats, through the mechanisms of inducing neuroinflammation and oxidative stress, and impairing the serotonergic axis. SF could reduce both inflammatory factors and oxidative stress parameters to protect the serotonergic system and alleviate memory impairment and depressive-like behavior in rats. These results provided insights into the biological mechanisms underlying the clinical link between depressive disorder and AD, and offered new drug options for the treatment of depressive symptoms in dementia.