Natural extracts are broadly utilized as remedies, nutrition additives, cosmetics or flavors as well as natural pesticides, fungicides or herbicides. Green manufacturing technologies are of added market value and are sustainable towards the climate neutrality politically demanded for 2045. The concept of digital twins involves experimentally distinct validated process models combined with process analytical technology that is to be adapted to the existing operations. This is a key technology for the autonomous operations in industry 4.0. This paper exemplifies this approach and evaluates the results of the application and implementation efforts of regulated industries. A conductivity sensor for the measurement of the dry residue content and/or Fourier-transformed infrared spectroscopy for marker/lead or reference substance concentration determination are the most feasible and straight forward solutions. Different process control concepts from simple PID controllers (proportional, integral and differential) to advanced process control using digital twin models are evaluated and discussed in terms of industrialization efforts and benefits. The global warming potential CO2 equivalent per kg of natural product could be decreased by a factor of 5−10 as well as the cost of goods, which makes the pay-out time for the industrialization investment less than 1 year and the approach highly competitive. The success rate of the extraction process under regulatory constraints can be raised to 100%, reducing waste, overall solvent consumption, personnel efforts and energy requirements to a minimum.