Background: Loss of fat-free mass (FFM) is associated with an increase in morbidity and mortality in cystic fibrosis (CF) patients. Handgrip strength (HGS) measures muscle function and may be associated with clinical parameters with prognostic value. Our objectives were to evaluate muscle strength through HGS in CF patients and to determine if there are any associations with respiratory clinical variables, FFM, and bone mineral density (BMD). Methods: A cross-sectional study conducted in clinically stable patients. We evaluated muscle function through HGS, respiratory function—forced expiratory volume in 1 s (FEV1) (%), forced vital capacity (FVC) (%), bronchorrhea, annual exacerbations, and body composition (FFM and FFM index, FFMI: fat-free mass in kg/height in m2) and Bone Mineral Density (BMD) through densitometry (DXA). Results: The study included 53 CF patients (58.5% females, mean age 28.3 ± 8.1, body mass index (BMI) 21.7 ± 3.4). The mean values for dynamometry were 40.2 ± 8.1 kg in males and 23.1 ± 7.0 kg in women, being 20.8% below the 10th percentile. Patients with lower muscle strength showed significantly more exacerbations and lower FEV1% and FVC%, as well as lower BMI, worse BMD (g/cm2), T-score, and Z-score. A significant and positive correlation was found between the mean and maximum dynamometry values and age, FVC%, BMI, FFMI, FFM (kg), and BMD. Conclusions: For adults with CF, HGS is a practical tool for assessment of health status. Low values reflect poor nutritional status and are associated with poor respiratory function, low fat-free mass and low bone mineral density.