Currently, there is no reliable, non-destructive way to assess the maturity of cantaloupes (Cucumis melo L.). Here, we investigated the extent to which Raman spectroscopy can be used to determine cantaloupe maturity. Five cantaloupe cultivars were grown and harvested at 13, 26, and 39 days after anthesis. Raman spectra from cantaloupes were acquired and partial least-square discriminant analysis (PLS-DA) was used to predict maturity based on the collected spectra. The PLS-DA model predicted maturity with up to 100 % accuracy in the cultivars studied. HPLC analysis of lutein and β-carotene in cantaloupe rind showed an increase in the concentration of carotenoids with maturity. The same trend was observed in the vibrational bands originating from carotenoids in the acquired Raman spectra. Based on this, Raman spectroscopy can primarily detect the changes of carotenoids in different cultivars of cantaloupe rind, which can be used for non-invasive and non-destructive assessment of fruit maturity.