Background: Thyroid hormone profoundly influences metabolic processes. Hypothyroidism, a common endocrine disorder, can significantly impact skeletal muscle and renal function. In hypothyroidism, muscle involvement often manifests as myopathy with elevated serum creatine phosphokinase (CPK) levels, while renal effects may alter serum creatinine levels and glomerular filtration rate. However, the extent of these changes and their relationship to hypothyroidism severity, especially in subclinical cases, remains unclear. This study aimed to evaluate these parameters in overt and subclinical hypothyroidism and investigate their correlation with thyroid function. Materials and methods: This cross-sectional study included 150 patients with hypothyroidism attending the Medicine OPD at Gandhi Medical College and Hamidia Hospital, Bhopal. Patients were divided into two groups: Group A with overt hypothyroidism and group B with subclinical hypothyroidism, based on their thyroid function tests. Serum levels of thyroid-stimulating hormone (TSH), free T₃, free T₄, CPK, and creatinine were measured for all participants. Creatinine clearance was calculated using the Cockcroft-Gault formula. Statistical analysis included t-tests for group comparisons and Pearson correlation to assess relationships between variables. Results: Serum CPK levels were significantly higher in overt hypothyroidism compared with subclinical hypothyroidism (p < 0.001). Similarly, serum creatinine levels were significantly elevated in overt hypothyroidism compared with subclinical cases (p < 0.001). A positive correlation was observed between serum TSH and CPK (r = 0.435, p < 0.001) and between TSH and creatinine (r = 0.208, p = 0.011). Serum T₄ showed negative correlations with both CPK (r = –0.363, p < 0.001) and creatinine (r = –0.546, p < 0.001). Conclusion: This study demonstrates that both serum CPK and creatinine levels are significantly elevated in hypothyroidism, particularly in overt cases. The strong correlations between thyroid function tests and these parameters suggest that CPK and creatinine could serve as useful markers for assessing hypothyroidism severity and monitoring treatment response.