Background: Early intervention for subjective cognitive decline (SCD) is becoming increasingly important to prevent progression to Alzheimer's disease (AD). Despite the promising results observed in animal models of AD, the neuroprotective and cognitive-enhancing effects of Dendropanax morbiferus (DM) still need to be evaluated in individuals with cognitive decline. Objective: This 12-week, randomized, double-blind, placebo-controlled trial assessed the effects of DM leaf extracts on cognitive function in 85 individuals with SCD (KCT0006329, registered on July 7, 2021). Methods: Participants were randomly assigned to either the DM (n = 43) or the placebo (n = 42) group. Cognitive functions, including attention and memory, were assessed at baseline, 8 weeks, and 12 weeks. High-resolution T1-weighted magnetic resonance imaging was performed at the beginning and end of the study to evaluate cortical thickness. Changes in cognition and cortical thickness and their associations were evaluated. Results: The results demonstrated significant improvements in attention (p = 0.014), memory (p = 0.037), and global cognitive function (p = 0.001) in the DM group compared to the placebo group, accompanied by increased cortical thickness in the left lingual gyrus/cuneus (corrected p < 0.05). Furthermore, in the DM group, increased cortical thickness in this region was correlated with both memory (r = 0.422, p = 0.016) and global cognitive functions (r = 0.471, p = 0.007). DM was well-tolerated, with no adverse events reported. Conclusions: These findings suggest that DM may possess cognitive-enhancing properties for individuals with SCD.