N-Acetylcysteine (NAC), a well-known thiol-containing antioxidant, may alleviate the toxicity of poly (methyl methacrylate) (PMMA) bone cement through the inactivation of the monomer components in the cement by its sulfhydryl moiety. This study aimed to reveal the effects of the NAC on the polymerization heat, degree of conversion (DC), mechanical properties, and residual monomer release of PMMA bone cement. The addition of NAC (0, 0.25, 0.50, 0.75, and 1.00 wt%) to PMMA powder significantly reduced the maximum polymerization temperature and steadily delayed the setting time. The DC of all experimental PMMA bone cements reached as high as 91% after 7 days of incubation, as determined by Fourier transform infrared spectroscopy (FTIR). The experimental groups showed steady declines in flexural strength and surface hardness as a fraction of increasing NAC. Meanwhile, the mechanical properties of the experimental groups increased with the duration of time. The amount of methyl methacrylate (MMA) leached into deionized water was analyzed using high performance liquid chromatography (HPLC) and was found to increase with an immersion time up to 24 h, after which no subsequent change was observed. The results showed a linear correlation between the thermal and mechanical properties and the released MMA with the DCs of the experimental groups. The potential usefulness of NAC in developing more biocompatible PMMA bone cement for increased working performance was highlighted in this study.