Lactoferrin (LAT), a multi-functional protein involved in numerous physiological functions, and the medicinal plant Pelargonium sidoides DC (PEL), have been described for their anti-inflammatory properties. Because the main advantage of natural products consists in administering them in combination rather than as single compound, we aimed to understand whether the combination of PEL and LAT, herein PELIRGOSTIM, could still prove beneficial or additive/synergistic activities during inflammatory conditions. To pursue this goal, we used macrophagic cells (J774.1) and treated them with PEL and LAT in a concentration-dependent manner. We found that PELIRGOSTIM was able to reduce the levels of reactive oxygen species (ROS) and nitrite, effects that were correlated to the release of lower levels of IL-1β after LPS treatment. In addition, the combination of PEL and LAT showed bacteriostatic activities against S. aureus and E. coli which had limited growth starting from 5 hours up to 20 hours. This effect was stronger than that observed for penicillin/streptomycin. Our results provide PELIRGOSTIM as an innovative combination of natural products capable to prevent inflammation-, oxidative stress- and microbial-related disorders.