The aim of the study was to assess the impact of manual lymphatic drainage (MLD) on the parameters of carbohydrate metabolism, lipid metabolism and the level of selected adipokines and cytokines in people with abnormal body mass index (BMI). In addition, an attempt was made to assess the optimal cut-off values of serum concentrations of the biochemical parameters studied in identifying the risk of obesity and insulin resistance (IR). The study included 60 subjects who underwent 10 and 30 min long MLD sessions three times a week. The study group included 15 patients with a normal body mass index (group I;n= 15), overweight patients (group II;n= 15) and obese patients (group III;n= 10). The control group was IV;n= 20 subjects not undergoing MLD. Biochemical tests were carried out on all subjects at stage 0′ (before MLD therapy) and at stage 1′ (one month after MLD therapy). In the control group, the time between the sample collection at stage 0′ and stage 1′ was the same as in the study group. Our results showed that 10 MLD sessions may have a positive effect on the selected biochemical parameters, including insulin, 2h-PG, leptin and HOMA-IR values in normal weight and overweight patients. In addition, in the study group, the highest AUCROCvalues in identifying the risk of obesity were found for leptin (AUCROC= 82.79%; cut-off = 17.7 ng/mL;p= 0.00004), insulin (AUCROC= 81.51%; cut-off = 9.5 µIU/mL;p= 0.00009) and C-peptide (AUCROC= 80.68%; cut-off = 2.3 ng/mL;p= 0.0001) concentrations as well as for HOMA-IR values (AUCROC= 79.97%; cut-off = 1.8;p= 0.0002). When considering the risk of IR, we observed the highest diagnostic value for insulin (AUCROC= 93.05%; cut-off = 1.8 ng/mL;p= 0.053), which was followed by C-peptide (AUCROC= 89.35%; cut-off = 17.7 ng/mL;p= 0.000001), leptin (AUCROC= 79.76%; cut-off = 17.6 ng/mL;p= 0.0002) and total cholesterol (AUCROC= 77.31%; cut-off = 198 mg/dL;p= 0.0008). Our results indicate that MLD may have a positive effect on selected biochemical parameters, including insulin, 2h-PG, leptin and HOMA-IR, in normal weight and overweight patients. In addition, we successfully established optimal cut-off values for leptin in the assessment of obesity and insulin in the assessment of insulin resistance in patients with abnormal body mass index. Based on our findings, we hypothesize that MLD, when combined with caloric restriction and physical activity, may serve as an effective preventive intervention against the development of obesity and insulin resistance.