Background In older patients with polypharmacy and multiple comorbidities, even low grades of statin-associated muscle symptoms may have clinical implications. The aim of this study was therefore to investigate the potential associations between statin use and measures of physical performance and muscle function. Methods Participants were aged 70+, treated with at least seven regular systemic medications, and not expected to die or become institutionalized within 6 months. Physical performance measured as gait speed and Short Physical Performance Battery (SPPB) score, and muscle function measured as grip strength, were compared between users and non-users of statins. In the subgroup of statin users, the dose-response relationship was assessed using harmonized simvastatin equivalents adjusted for statin potency, pharmacokinetic interactions and SLCO1B1 c.521 T > C genotype. Multiple linear regression analyses were applied to investigate potential associations between stain use and exposure as independent variables, and physical performance and muscle function as outcomes, adjusted for age, gender, body mass, comorbidity, disability and dementia. Results 174 patients (87 users and 87 non-users of statins) with a mean (SD) age of 83.3 (7.3) years were included. In analyses adjusted only for gender, grip strength was significantly higher in users than in non-users of statins [regression coefficient (B) 2.7, 95% confidence interval (CI) 1.0 to 4.4]. When adjusted for confounders, the association was no longer statistically significant (B 1.1, 95% CI − 0.5 to 2.7). SPPB and gait speed was also better in statin users than in non-users, but the differences were not statistically significant. In dose-response analyses adjusted for confounders, we found a statistically significant increase in SPPB score (B 0.01, 95% CI 0.00 to 0.02) and gait speed (B 0.001, 95% CI 0.000 to 0.002) per mg increase in simvastatin equivalents. Conclusions In contrast to our hypothesis, statin use and exposure was associated with better measures of physical performance and muscle function in older patients with complex drug treatment. The unexpected findings of this cross-sectional, observational study should be further investigated by comparing physical performance before and after statin initiation or statin withdrawal in prospective studies. Trial registration ClinicalTrials.gov identifier: NCT02379455, registered March 5, 2015.