You can yes, plugins will typically add settings groups that contain settings for the plugin, then if you call rebuild_settings() it will re-generate the settings.php file
$settings_group = array(
"name" => "myplugin",
"title" => "My Plugin Settings",
"description" => "Settings for my plugin.",
"disporder" => "10",
"isdefault" => 0
);
$db->insert_query("settinggroups", $settings_group);
$gid = $db->insert_id();
$insert = array(
"name" => 'mysetting',
"title" => 'My Setting',
"description" => 'This setting does something cool',
"optionscode" => 'yesno',
"value" => 1,
"disporder" => 1,
"gid" => intval($gid),
);
$db->insert_query("settings", $insert);
rebuild_settings();
You could then use $mybb->settings['mysetting'] to access the value of that setting.