Background Serotonin (5-HT) precursors regulate bone remodeling. This study aims to investigate the correlation of plasma 5-HT precursors and metabolite with bone mineral density (BMD) and bone turnover markers in postmenopausal osteoporosis (PMOP) patients. Methods The age, body mass index (BMI), and years since menopause (YSM) were documented for 348 postmenopausal women in normal/osteopenia/osteoporosis (OP) groups, with lumbar spine and femoral neck BMD measured. Serum bone turnover markers (PINP/β-CTX) and plasma 5-HT, 5-HT precursors (Trp/5-HTP) and metabolite (5-HIAA) were measured by ELISA. OP patients were allocated to high/low expression groups following ROC analysis of 5-HT/Trp/5-HTP/5-HIAA. The relationship of plasma 5-HT/Trp/5-HTP/5-HIAA, BMD, and bone turnover markers with PMOP was analyzed using logistic regression analysis. The correlation of plasma 5-HT/Trp/5-HTP/5-HIAA with BMD and bone turnover markers was analyzed using Pearson’s correlation analysis, followed by logistic regression analysis of the relationship between plasma 5-HT/Trp/5-HTP/5-HIAA and BMD, bone turnover markers and PMOP. Results BMI, YSM, BMD and PINP, and β-CTX levels differed among groups. Levels of plasma 5-HT precursors/metabolite were increased in OP patients. Individuals with high 5-HT precursors/metabolite levels had low BMD and high PINP/β-CTX levels. The 5-HT precursors/metabolite negatively-correlated with BMD and positively-correlated with PINP/β-CTX. BMI, YSM, BMD, and PINP/β-CTX/Trp/5-HTP/5-HT related to PMOP and were independent risk factors for OP. Conclusion Plasma 5-HT precursors and metabolite negatively-correlate with BMD and positively-correlate with PINP/β-CTX in PMOP patients. Peripheral 5-HT precursors and metabolite level may be a new direction of treatment of PMOP and bone metabolism-related disorders.