Fiber reflectance spectroscopy is a non-invasive method for diagnosing skin diseases or evaluating aesthetic efficacy, but it is dependent on the inverse model validity. In this work, a lookup-table-based inverse model is developed using two-layered Monte Carlo simulations in order to extract the physiological and optical properties of skin. The melanin volume fraction and blood oxygen parameters are extracted from fiber reflectance spectra of in vivo human skin. The former indicates good coincidence with a commercial skin-melanin probe, and the latter (based on forearm venous occlusion and ischemia, and hot compress experiment) shows that the measurements are in agreement with physiological changes. These results verify the potential of this spectroscopy technique for evaluating the physiological characteristics of human skin.