Knee osteoarthritis (KOA) has a high incidence among the elderly, significantly impacting their quality of life and overall health. Medial unicompartmental knee arthroplasty (UKA) is an excellent choice for treating knee single-compartment lesions, and lower limb alignment has a profound impact on medial UKA. To explore the influence of different lower limb alignments on medial UKA. In this study, we selected MR and CT data of healthy adult male knee joints to establish a complete finite element analysis (FEA) model of the knee joint. After validation, we established a finite element model of medial UKA. Subsequently, we created 60 sets of FEA models with different lower limb alignments to analyze the impact of different lower limb alignments on medial UKA. A vertical load of 1000 N was applied to the FEA models with different lower limb alignments. During the process of shifting the Mikulicz line from the midpoint of the knee joint towards the medial side, the lower limb load was primarily concentrated on the medial compartment. The stress values of the lateral meniscus, tibial cartilage, and femoral cartilage gradually decreased. ROI (region of interest) 1 and ROI 2 showed the maximum principal strain changes, while ROI 3 and ROI 4 exhibited less pronounced fluctuations, with the maximum principal strain roughly proportionally increased. During the process of shifting the Mikulicz line towards the lateral side from the midpoint of the knee joint, the stress on the lateral compartment increased observably. ROI 1, ROI 2, ROI 3, and ROI 4 showed decreased maximum principal strains, approximately inversely proportional changes, but the overall reduction was relatively small. Different lower limb alignments have a profound impact on the short- and long-term joint function after UKA. When the Mikulicz line is 10 mm inside the midpoint of the knee joint or slightly outside, there is a relatively lower risk of tibial component fractures, lower stress on the lateral compartment, and lower load on the prosthesis. During medial UKA, measures such as bone resection and prosthesis selection should be taken to ensure that the Mikulicz line is in the ideal position.