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This study evaluated handgrip strength (HGS), circulating homocysteine levels and related factors in postmenopausal women. This study is a sub-analysis of a prospective cohort of 303 postmenopausal women aged 62.7 ± 6.9 years who had HGS measures with a digital dynamometer as the primary outcome, and plasma homocysteine and creatinine levels and glomerular filtration rate (GFR) measures as the secondary outcomes. The average HGS was 22.5 ± 4.0 kg, 29.4% of women had dynapenia (HGS < 20 kg), adiposity was 40.3 ± 5.4% and 9.57% of women had hyperhomocysteinemia (homocysteine >15 μmol/l). There were no differences between tertiles of homocysteine and HGS (p = 0.641). Plasma homocysteine levels were unrelated to HGS (r = −0.06) and correlated with age (r = 0.17), GFR (r = −0.28) and creatinine (r = 0.23). Hyperhomocysteinemia was not associated with HGS (odds ratio [OR] = 0.98 [95% confidence interval (CI): 0.89; 1.08]) or dynapenia (OR = 1.10 [95% CI: 0.45; 2.47]). The risk of presenting low HGS were not significantly associated with homocysteine (OR = −0.08 [95% CI: −0.21; 0.06]) and were associated with age (OR = −0.23 [95% CI: −0.29; −0.17]), adiposity (OR = −6.52 [95% CI: −9.53; −3.50]) and creatinine (OR = 6.22 [95% CI: 2.48; 9.97]). HGS and dynapenia were unrelated to hyperhomocysteinemia. Age, GFR and creatinine were significantly associated with plasma homocysteine levels. [ABSTRACT FROM AUTHOR]