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Background: Phenolic compounds are one of the main groups of secondary metabolites responsible for multiple biological and pharmacological properties that play a vital role in improving human health quality. Encapsulation by spray dryer creates protection toward the phenolic compounds as an efficient way for increasing product performance. Method: The phenolic compounds of Satureja khuzistanica Jamzad (SKH) and S. rechingeri Jamzad (SRH) were enriched based on adsorbent resin column chromatography and the enrichment index was confirmed by HPLC-UV analysis. Gum Arabic, carboxylated chitosan, and pectin with the optimum percentage of 1% w/w used to encapsulate SKH and SRH by the spray drying technique. Result: Encapsulation yield was 38.18 – 59.00 %, particle size ranged 2.278 - 4.689 µm, and release time was between 4.08 - 82.08 min. The gum Arabic-based capsules showed the fastest and pectin-based revealed the slowest release time. The best statistical model explained a release mechanism was Korsmeyer model. Anomalous transport was observed from all formulas except SKH-gum Arabic (case-I transport), SKH-pectin, and SRH-carboxylated-chitosan (super case-II transport). The cytotoxic activity of encapsulate SKH’s revealed reducing the viability of AGS evaluated by the MTT compared with SRH’s. Conclusion: Encapsulation by spray drying has proven to be a promising technique to improve the bioavailability, release time, and mechanism of functional polyphenolic compounds as medicines, food supplements, and food additives.