Background <p>The causal relationship between keloid and mental disorders remains unclear. The aim of this study was to investigate whether keloid was causally associated with the risk of bipolar disorder (BD), anxiety, schizophrenia (SCZ), major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) using a bidirectional Mendelian randomization (MR) analysis.</p> Methods <p>The large available genome-wide association study (GWAS) dataset of keloid, BD, anxiety, SCZ, MDD and PTSD was used for summary statistics. The bidirectional MR analyses were performed using a variety of methods of analysis including inverse variance weighting, MR-Egger regression, weighted median, simple modal and weighted modal methods. Sensitivity analyses were conducted using Cochran’s Q to estimate heterogeneity, and the MR-Egger method was used to estimate horizontal pleiotropy.</p> Results <p>MR analysis showed that keloid susceptibility was associated with an increased risk of BD (OR = 1.027, 95% CI: 1.005–1.049, <i>p</i> = 0.015) and SCZ (OR = 1.023 (95% CI: 1.006–1.040, <i>p</i> = 0.006). We also observed a negative association between keloid and PTSD (OR = 0.903, 95% CI: [0.835–0.977], <i>p</i> = 0.011). There was no evidence for a causal relationship between keloid and anxiety (OR = 0.982, 95% CI: 0.961–1.004, <i>p</i> = 0.110) and MDD (OR = 0.997, 95% CI: 0.987–1.006, <i>p</i> = 0.476). Reverse MR analysis revealed that there was no causal relationship between keloid and the mental disorders.</p> Conclusion <p>This study provides evidence that there is a link between BD, SCZ, PTSD and keloid. However, there was no causal relationship between anxiety, MDD and keloid. This study may provide important clues and references for the study of keloid and mental disorders. We urge that the mental conditions of keloid patients should be taken into account in clinical practice and that necessary psychological support should be provided.</p>