The mold Monascus has been used as a natural food coloring agent and food additive for more than 1000 years in Asian countries. In Chinese herbology, it was also used for easing digestion and antiseptic effects. Through a thorough investigation of a citrinin-free strain: M. purpureus BCRC 38110, four azaphilones, three benzenoids, one benzofuranone, one 5′,6′-dihydrospiroisochromane-1,2′-pyran-4′(3′ H )-one derivative, two steroids, and six tetralones have been successfully identified. Among them, monapyridine A ( 1 ), monatetralones A-E ( 2-6 ), and monabenzofuranone ( 7 ) were first reported. Their structures were characterized by 1D and 2D NMR, UV, IR, and HRESIMS analyses. With a series of bioactivity screening, monascuspirolide B ( 14 ) and ergosterol peroxide ( 16 ) exhibited concentration-dependent attenuation of the paclitaxel-induced neurite damage of mouse dorsal root ganglion neurons. The interleukin (IL)-1β-induced release of inflammatory cytokines IL-8 and tumor necrosis factor (TNF)-α in human chondrosarcoma cells was inhibited by monapurpureusone ( 8 ) and monascuspirolide B ( 14 ). Altogether, M. purpureus BCRC 38110 possessed potentials as natural therapeutics against inflammatory osteoarthritis and paclitaxel-induced neurotoxicity. Seven new and ten known compounds were isolated from a citrinin-free strain: M. purpureus BCRC 38110. The bioactivity results indicated that this strain possessed potentials against inflammatory osteoarthritis and paclitaxel-induced neurotoxicity.