Inflammation is a normal response in defense to agents that may cause damage to the human body. When inflammation becomes chronic, reactive oxygen species (ROS) are produced; which could lead to diseases such as cancer. The aim was to assess liposomes’ antioxidant and anti-inflammatory capacity loaded with amaranth unsaponifiable matter and soybean lunasin (UM + LunLip) in an in vitro model using fibroblasts and macrophages. To evaluate ROS production, fibroblasts CHON-002 ABAP were added to promote ROS production; and the cells were treated with UM + LunLip. For inflammation markers production, lipopolysaccharides (LPS)-stimulated RAW 264.7 and peritoneal macrophages were treated with empty liposomes (EmLip), liposomes loaded with unsaponifiable matter (UMLip), liposomes loaded with lunasin (LunLip), and UM + LunLip. ROS production was significantly decreased by 77% (p < 0.05) when fibroblasts were treated with UM + LunLip at 2 mg lunasin/mL compared with the control treated with ABAP. Treatment with UMLip was the most effective in reducing tumor necrosis factor-α (71–90%) and interleukin-6 (43–55%, p < 0.001). Both liposomes containing unsaponifiable matter (UMLip and UM + LunLip) were more effective than EmLip or LunLip. In conclusion, amaranth unsaponifiable matter-loaded liposomes are effective in decreasing pro-inflammatory cytokine production.