An efficient and sustainable expanded‐bed adsorption (EBA) method was developed for the valorization of lotus leaf which is an agricultural by‐product. The in‐situ procedure was used to reduce the energy consumption of EBA. Comparing this in‐situ process to the conventional one, some additional advantages were observed, namely, significant enhancement of nuciferine recovery, considerable reduction of processing time, etc. Furthermore, a multistage procedure was investigated to reduce running cost and minimize environmental pollution by reusing solvents and adsorbents. Reusing of D101 macroporous resin, HCl and NaOH solution had almost no influence on the yield of nuciferine.