Acne is a dermatological condition that importantly affects individuals of all ages, especially during puberty. The potency of Houttuynia cordata Thunb. Against this disease has been mentioned in many studies. Nevertheless, its application still remains limited due to its instability and absence of a marketable formulation with relevant scientific proof. This study focused on the formulation study and evaluation of a lotion from H. cordata leaf extract for acne treatment. The raw material was first controlled to ensure its quality and then extracted using the hot process method. Different formulations of lotion containing H. cordata extract were prepared by changing the type and ratio of emulsifier and thickener. The finalized lotion was assessed for its quality aspects (appearance, consistency, stability), tested for its antibacterial activity against Propionibacterium acnes and Streptococcus epidermidis, its antioxidant properties using SET and HAT assays, and its anti-inflammatory assay using the NO radical scavenging assay. Raw materials and H. cordata leaf extracts complied with the standards of the corresponding monograph in Taiwan Pharmacopoeia. The finalized lotion, with 5% tween 60 and 5% HPMC, met all expected quality criteria. Furthermore, the lotion demonstrated high stability and potent biological properties against acne (including antibacterial, antioxidant, and anti-inflammatory activities). A lotion containing H. cordata extracts with relevant quality standards and potent activities against acne was successfully developed in this study. These findings provide a foundation for future research and the preparation for clinical trials to better apply this natural source in acne treatment.