Naturally produced sandalwood oil (N-SWO) is prized for its use, both in perfumery as well as for skin benefits. However, its availability has been severely restricted in recent years due to overexploitation. The industry has responded by using biotechnology to produce santalol—the key molecule in N-SWO. Using such biotechnology-derived and natural ingredients, an oil that mimics the composition of N-SWO was created. This reconstituted oil called Sacrosantola was compared to N-SWO for its safety and skin benefits, using various in vitro models. Compared to N-SWO, Sacrosantol showed a similar safety profile, photo-protective and anti-inflammatory benefits, as well as antibacterial properties. Thus, Sacrosantol can be used as a sustainable and cost-effective alternative to natural sandalwood oil.