Abstract Background Thyroid diseases are the most common endocrine disorders worldwide. Thyroid hormones are essential for lipid synthesis, metabolism, and mobilization. Lipid levels in the blood may be altered when there is thyroid dysfunction. Lipid changes are linked to hyperthyroidism and primarily involve total and low-density lipoprotein cholesterol. The serum lipid profile is negatively impacted by hypothyroidism, which may increase the risk of atherosclerotic disease development. Thus, hypothyroidism constitutes a significant cause of secondary dyslipidemia. However, the results obtained from different studies are inconsistent, and there are few data regarding lipid profiles in thyroid dysfunction patients in the study area. Therefore, this study aimed to assess the lipid profile of thyroid dysfunction patients at Wolaita Sodo University Comprehensive Specialized Hospital from May 1 to June 15, 2021. Methods A comparative cross-sectional study was conducted involving 200 participants (100 thyroid dysfunction patients and 100 age- and sex-matched controls). Socio-demographic and related data were collected from the study participants via a pretested structured questionnaire through face-to-face interviews. Independent sample T tests and Mann‒Whitney U tests were used for data analysis. P