Learn Spanish (Latin America): El autobús está lleno de personas.

We use de here because the phrase is lleno de (full of), which matches English perfectly. While you use en to talk about your location on the vehicle (Estoy en el autobús), when you describe what is taking up the space inside it, you use de.

Why do we use está instead of es?

We use está (from the verb estar) because being full is a temporary condition or state. If you used es (from the verb ser), it would sound like being full of people is a permanent, built-in physical characteristic of the bus.

Why is it lleno ending in "-o" when personas is feminine?

The adjective lleno (full) describes el autobús (the bus), which is a masculine noun. Adjectives always match the gender of the noun they are actually describing, regardless of the other nouns that come later in the sentence.

Could I use the word gente instead of personas to say "people"?