The research on compounds exhibiting photoprotection against ultraviolet radiation (UVR) is a matter of increasing interest. The methanolic extract of a cell culture of Buddleja cordata has potential photoprotective effects as these cells produce phenolic secondary metabolites (SMs). These metabolites are attributed with biological activities capable of counteracting the harmful effects caused by UVR on skin. In the present work, the methanolic extract (310–2500 µg/mL) of B. cordata cell culture showed a photoprotective effect on UVB-irradiated 3T3-Swiss albino fibroblasts with a significant increase in cell viability. The greatest photoprotective effect (75%) of the extract was observed at 2500 µg/mL, which was statistically comparable with that of 250 µg/mL verbascoside, used as positive control. In addition, concentrations of the extract higher than 2500 µg/mL resulted in decreased cell viability (≤83%) after 24 h of exposure. Phytochemical analysis of the extract allowed us to determine that it was characterized by high concentrations of total phenol and total phenolic acid contents (138 ± 4.7 mg gallic acid equivalents and 44.01 ± 1.33 mg verbascoside equivalents per gram of extract, respectively) as well as absorption of UV light (first and second bands peaking at 294 and 330 nm, respectively). Some phenylethanoid glycosides were identified from the extract.