Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary gland consisting of three main histological components: mucocytes, intermediate and epidermoid cells. Various grading systems (AFIP, Brandwein, modified Healy, MSKCC) are difficult to use. The Ki-67 and GLUT1 markers associated with tumor aggressiveness can improve MEC diagnosis and classification. The study aimed to assess the correlation of the cell proliferative activity and glucose metabolism with the MEC grading systems. Tumors of a total of 40 patients with MEC were analyzed and determined in accordance with the following grading systems: AFIP, Brandwein, modified Healy, and MSKCC. Immunohistochemistry (IHC) was used to estimate Ki-67 proliferation indices and GLUT1 expression intensity. IHC showed high Ki-67 indices and GLUT1 values in epidermoid and intermediate cells, while mucocytes showed low or no expression. There were significant differences in Ki-67 and GLUT1 expression between epidermoid (p < 0.005) and intermediate cells (p < 0.01). Comparison revealed the increase between grades 1 and 2, 1 and 3, but no differences between grades 2 and 3. Spearman’s rank correlation test revealed moderate positive correlations with tumor grades for GLUT1 and Ki-67, and the AFIP system showed the highest correlation (Ki-67: rs = 0.55; GLUT1: rs = 0.50). Thus, GLUT1 and Ki-67 are most intensely expressed in epidermoid and intermediate cells showing a strong correlation with the tumor grade and aggressiveness, especially in low-grade and intermediate-grade MEC. These markers can improve the diagnosis of MEC malignancy degree. The AFIP system most closely matches these markers in epidermoid and intermediate cells.