The "Shuanghuanglian" formula, simplified from the classic formula "Yin Qiao San", is composed of the Honeysuckle flower, Scutellaria root and Forsythia fruit. Its primary effects include dispelling wind, relieving exterior syndrome, and clearing heat and toxic materials. The traditional "Shuanghuanglian" (SHL) preparation method requires prolonged heating that results in the loss of volatile oil components and diminishes its efficacy. This study centered on developing an enhanced "Shuanghuanglian" volatile oil-infused soluble powder (SHLO) and evaluating its therapeutic efficacy and mechanisms using a mouse pneumonia model. Our findings demonstrate that SHLO administration significantly restores lung tissue damage and mitigates LPS-induced pulmonary inflammation. SHLO intervention led to a notable reduction in TUNEL-positive lung cells and levels of IL-6 (P<0.01), IL-1β (P<0.001), and TNF-α (P<0.05) in bronchoalveolar lavage fluid (BALF) triggered by LPS. Furthermore, SHLO markedly suppressed p-ERK levels without substantially influencing p-JNK levels or p-NF-κB p65 levels. The relative traces of p-ERK, MyD88, and TLR4 in lung tissues were notably decreased in the SHLO group relative to the LPS group. Additionally, SHLO reduced the proportion of an unclassified Muribaculaceae genus while increasing Akkermansia levels in the gut microbiota. In summary, SHLO effectively defends against LPS-induced lung damage through the inhibition of the TLR4/MyD88 and p-ERK signaling pathways and modulating gut microbiota.