Background <p>Numerous studies have indicated that optical coherence tomography (OCT) can serve as a valuable tool for assessing cognitive ability by measuring changes in ocular macular thickness. Recently, gender differences in the association between retinal thickness and cognitive function have been suggested. However, it remains unclear whether such gender differences exist in the elderly Chinese.</p> Methods <p>This study utilized cross-sectional data from the Rugao Aging Cohort in 2019, comprising 734 healthy elderly individuals. Macular thickness was measured using OCT, while cognitive function was assessed using the Mini-Mental State Examination (MMSE), the Hierarchical Dementia Scale (HDS), and the Montreal Cognitive Assessment (MoCA). Comparative t-tests were employed to evaluate differences in macular thickness between elderly males and females, and multiplelinear regression analyses were conducted to examine the association between ocular macular thickness and cognitive function in males and females separately.</p> Results <p>Our findings revealed significant differences in all macular layers’ thickness between males and females, that males exhibited a thicker inner ring (<i>P</i> ≤ 0.026) and a thinner outer ring <i>(P</i> ≤ 0.024) compared to females. Cognitive function as assessed by MMSE, MoCA, and HDS exhibited significant associations with the central thickness and the average thickness of each region of all macular layers within the inner macular ring among the elderly participants (β ≥ 0.202, <i>P</i> ≤ 0.045). However, upon gender stratification, we only observed significant associations between cognitive function and the average thickness of the inner macular ring (including the inner temporal, inner nasal, inner superior, and inner inferior regions) of all macular layers (β ≥ 0.333, <i>P</i> ≤ 0.055) in females, instead of in males (β ≥ -0.254, <i>P =</i> 1). Additionally, the significant association between MoCA score and central macular thickness was observed exclusively in females (β = 0.529, <i>P</i> = 0.027).</p> Conclusions <p>In the Rugao Aging Cohort, significant gender differences of thickness of all macular layers between males and females were identified, with males exhibiting thicker inner rings and thinner outer rings compared to females. Notably, cognitive decline was associated with the thinning of the central part and inner ring of macula exclusively in females. These results suggest that when macular thickness is used as a risk marker for cognitive decline, its gender bias should be carefully considered.</p>