BACKGROUND: Pigmented rice is rich in coloured molecules known as anthocyanins, which exhibit a strong antioxidant activity and are used as additives to improve both the aspect and nutraceutical value of food. RESULTS: In this work, Nerone Gold 26/6 was employed as raw material for the extraction of antioxidants varying solvents and the operating conditions by evaluating three different techniques, i.e., (1) conventional solid–liquid extraction, (2) high pressure and temperature extraction, and (3) ultrasound‐assisted extraction. The quality of extracts was assayed by determining their total polyphenol yield, total flavonoid yield, total anthocyanin yield, and the antioxidant activity by spectrophotometric analyses, as well as the phenolic profile by high performance liquid chromatography. High pressure and temperature extraction presented the highest content of polyphenols (14.0 ± 1.10 mggₐₗₗᵢc ₐcᵢd ₑqᵤᵢᵥₐₗₑₙₜₛ/gdᵣᵢₑd bᵢₒₘₐₛₛ) using a green solvent as ethanol 70% (v/v), while ultrasound‐assisted extraction carried out for 20 min showed the highest anthocyanin content (7.5 ± 0.94 mgₘₐₗᵥᵢdᵢₙ ₑqᵤᵢᵥₐₗₑₙₜₛ/gdᵣᵢₑd bᵢₒₘₐₛₛ). Both of the extracts were biologically validated on human endothelial cells. CONCLUSION: Among the non‐conventional techniques, high pressure and temperature extraction at 60 °C and ultrasound‐assisted extraction for 20 min provided high total polyphenol, flavonoid, and anthocyanin yields and antioxidant activities compared to solid–liquid extraction. Both extracts were well tolerated by endothelial cells in a concentration ranging from 0.0125 to 0.0500 mggₐₗₗᵢc ₐcᵢd ₑqᵤᵢᵥₐₗₑₙₜₛ/mLₑₓₜᵣₐcₜ. Finally, solid phase extraction was responsible of a further increase of the extract biocompatibility. © 2021 Society of Chemical Industry (SCI).