The question of the effect of NSAIDs on the functional state of the thyroid gland arises due to the existence of conflicting studies on the various effects of drugs, in particular NSAIDs on thyroid hormones in the serum. It is known that drugs can affect the hormonal activity of the thyroid gland in various ways, in particular through the induction of cytochromes, direct influence on the synthesis and secretion of hormones or their metabolism, clearance and uptake by tissues, antagonism with transport proteins. The aim of the study was to investigate the effects of NSAIDs and paracetamol on the functional state of the thyroid gland in osteoarthritis with hypothyroidism. The study was performed on 80 nonlinear white rats with reconstituted osteoarthritis and hypothyroidism. To address the question posed about the effect of NSAIDs and paracetamol on the functional state of the thyroid gland, which was determined by the level of hormones TSH, T3 and T4, each of the studied drugs was administered in two doses. Doses were chosen based on calculations based on average and maximum human doses, using a species sensitivity factor, and taking into account data from the literature. Interpretation of the results obtained was based on the known fact that clinical laboratory diagnosis of hypothyroidism is characterized by increased concentration of TSH and decreased content of free T4, while the concentration of free T3 remains within the normal range or sometimes decreases. The conducted study revealed that analgesic drugs exhibit a variety of effects on thyroid function in conditions of comorbid pathology, which depends on both the drug itself and its dose. The authors have identified drugs that can adversely affect hormone concentration in a dose-dependent manner. Thus, ibuprofen (7 mg/kg), meloxicam (12 mg/kg) and nimesulide (100 mg/kg) reduced the TSH level and increased the serum T4 level in rats, which aggravated hypothyroidism. It was proved that pharmacotherapy of osteoarthritis against the background of hypothyroidism should take into account the effect of analgesics on the hormones of TSH, T3 and T4, which should be kept in mind while correcting the functional activity of the thyroid gland.