Abstract Background Effective evaluation or prediction of therapy response could be helpful for treatment of chronic kidney disease (CKD), which may rely on accurate biomarkers. Acylcarnitines are involved with lipid metabolism and mitochondrial function. The relation of acylcarnitines with treatment response in patients with CKD is unknown. The purpose of this study is to investigate the association of plasma acylcarnitines with renal function and its alteration by intervention in patients with IgA nephropathy (IgAN). Methods A retrospective study was performed in 81 IgAN patients with treatment by traditional Chinese medicine (TCM). Multivariate linear regression analyses were performed to identify the association of acylcarnitines with baseline estimated glomerular filtration rate (eGFR) and eGFR changes after treatment. Results Twenty-seven acylcarnitines were measured at baseline and after 1-year TCM intervention. Certain short-chain and median-chain acylcarnitines were independently associated with baseline eGFR and eGFR alterations after 1 year treatment. Particularly, patients with high C5:1(β = − 0.42), C8:1(β = − 0.49), C3DC(β = − 0.5), C10:1(β = − 0.36) and C5DC(β = − 0.64)at baseline would have worse prognosis and treatment response. Moreover, certain acylcarnitines could be changed along with the eGFR alteration after 1-year TCM treatment. Conclusions The findings indicate a significant association between plasma acylcarnitines with prognosis and treatment responses in patients with IgAN, which suggest its role as a potential penal of biomarker for IgAN.