Poly phenols are multifunctional secondary metabolites in plants. Less information is available concerning the statistical yield, optimal extraction method and pharmacological activity with regards to active compounds from Pelargonium graveolens LʼHér leaf. Therefore, Box-Behnken design was used to optimize extraction parameters such as the speed of agitation (rpm), the volume of methanol solvent (mL), time of extraction (h) and mass of plant material (g). A polynomial quadratic model produced satisfactory fitting of experimental data: % yield (Y): R 2 = 0.9943, total phenols (TPC): R 2 = 0.9621 and total flavonoids (TFC): R 2 = 0.9873 at p < 0.05. The antioxidant activities of optimized methanol extract and controls were evaluated by DPPH, ABTS scavenging, and ferric reducing power in vitro assays. The kinetics of the lipid protective activity was studied and fitted into a pseudosecond-order kinetic model. Total antioxidant capacity (TAC) of the extract and gallic acid showed donating potential of 0.35 ± 0.10 mg QE/g and 0.35 ± 0.10 mg QE/g, respectively. The best MIC value of 1.56 mg/mL was against E. coli. The cell proliferation and cytotoxic activities of the extracts were evaluated using the Cell Titer® blue cell viability and lactate dehydrogenase assay on HaCaT cells. Bioactive compounds present in the leaf of P. graveolens were identified by GC-MS analysis by methanol extract.