May, June, and September are the best months: warm enough for the beach at Agios Isidoros, but without the full heat and crowds of July and August. The town is quiet in winter — many tavernas and tourist facilities close — though the distilleries operate year-round and the old town can be explored at any time.
The Greek Orthodox Easter period (March or April) brings the local community together for celebrations that have a particular warmth in small towns like Plomari; if your timing allows, it is worth experiencing.