Cayo Guillermo consists of 3-4 all-inclusive hotels, many shrubs and birds, a boating station and absolutely nothing else. No Cubans reside in this region as it is a dedicated (and completely segregated) tourist location. Cayo Coco is similar, but more built up.
The local language is Spanish, but English is spoken in the hotels.
Most visitors arrive at the Jardines del Rey International Airport on the neighbouring Cayo Coco and then by road across the causeway connecting the two.
There is little to see other than the beach and the wildlife. Getting out into the real Cuba is highly recommended. A day trip to Moron or an overnight trip to Trinidad or Havana are some of the organised trips on offer.
Hotels have daily entertainment and organised excursions elsewhere in Cuba are available, but are quite expensive.
The safe in the rooms at some hotels in Cayo Guillermo are operated by the same key as the room. This could lead to your wallet being slightly lighter than it was when you put it in at the beginning of your holiday, as you won't need it for the duration of the all-inclusive stay. Somewhat annoying if you choose to tip the cleaner and find out on the bus back to the airport!