| Summary: | The chemical composition and antimicrobial activity of propolis from a semi-arid region of Morocco were investigated. Fifteen compounds, including triterpenoids (<b>1</b>, <b>2</b>, <b>7</b>–<b>12</b>), macrocyclic diterpenes of ingol type (<b>3</b>–<b>6</b>) and aromatic derivatives (<b>13</b>–<b>15</b>), were isolated by various chromatographic methods. Their structures were elucidated by a combination of spectroscopic and chiroptical methods. Compounds <b>1</b> and <b>3</b> are new natural compounds, and <b>2</b>, <b>4</b>–<b>6</b>, and <b>9</b>–<b>11</b> are newly isolated from propolis. Moreover, the full nuclear magnetic resonance (NMR) assignments of three of the known compounds (<b>2</b>, <b>4</b> and <b>5</b>) were reported for the first time. Most of the compounds tested, especially the diterpenes <b>3</b>, <b>4</b>, and <b>6</b>, exhibited very good activity against different strains of bacteria and fungi. Compound <b>3</b> showed the strongest activity with minimum inhibitory concentrations (MICs) in the range of 4–64 µg/mL. The combination of isolated triterpenoids and ingol diterpenes was found to be characteristic for <i>Euphorbia</i> spp., and <i>Euphorbia officinarum</i> subsp. <i>echinus</i> could be suggested as a probable and new plant source of propolis.
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