The Atherogenic Index of Plasma (AIP) is a novel metric linked to several diseases. However, there is inadequate evidence to investigate the relationship between AIP and depression. Therefore, we aim to elucidate the non-linear association between AIP and depression.12,453 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 were included. The AIP was calculated as log10 (triglycerides/high-density lipoprotein cholesterol). The Patient Health Questionnaire (PHQ-9) was used to identify depression (PHQ-9 ≥ 10). Weighted multivariate logistic regression, restricted cubic splines (RCS) models, subgroup analysis, and interaction tests were employed to reveal the relationship between AIP and depression.AIP was found to be significantly correlated with depression. In the fully adjusted model, elevated AIP levels were associated with higher odds of depression (odds ratio [OR] = 1.50; 95 % CI: 1.06-2.12). The RCS analysis indicated an L-shaped pattern in the relationship between depression and AIP, with inflection points at -0.289. Beyond this inflection point, individuals with elevated AIP levels were associated with higher odds of depression (OR = 2.25; 95 % CI: 1.49-3.39). Notably, the association was particularly pronounced among individuals with diabetes.This cross-sectional study is unable to establish causal relationships.There was an L-shaped association between AIP and depression among US adults. AIP has the potential value as a biological marker for depression, and maintaining AIP values below a certain threshold may help in managing depression.Copyright © 2024. Published by Elsevier B.V.