(1) Background: In hospitals, medical and dental clinics, antiseptics or disinfectants play an essential role in the control of nosocomial infections. This study aimed to evaluate R. officinalis and P. paniculata glycolic extracts regarding: (I) their antimicrobial action on planktonic and biofilm (monotypic and cutaneous biofilm model—S. aureus, S. epidermidis and C. acnes); and (II) their cytotoxicity on human keratinocytes (HaCaT). (2) Methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were performed (CLSI protocol M7-A6 and M11-A8). MTT analysis was used to evaluate the antibiofilm activity of the extracts on biofilms and their cytotoxicity on human keratinocytes. (3) Results: The combined glycolic extracts MIX A (75% P. paniculata + 25% R. officinalis); MIX B (50% P. paniculata + 50% R. officinalis); and MIX C (25% P. paniculata + 75% R. officinalis) promoted MBC values by 50 mg/mL on S. aureus, absent on S. epidermidis, and ranged 6.25–50 mg/mL for C. acnes. The cutaneous biofilm model was reduced more than 90%. In addition, it showed biocompatibility with human keratinocytes, resulting in percentages of viability greater than 50%. (4) Conclusions: The combination of extracts promoted antimicrobial action on planktonic cultures, and monotypic and heterotypic biofilms of skin pathogens. Additionally, these extracts are biocompatible against human keratinocytes.